Sample records for cell chips adapting

  1. Embedded Adaptive Optics for Ubiquitous Lab-on-a-Chip Readout on Intact Cell Phones

    Pakorn Preechaburana; Anke Suska; Daniel Filippini


    The evaluation of disposable lab-on-a-chip (LOC) devices on cell phones is an attractive alternative to migrate the analytical strength of LOC solutions to decentralized sensing applications. Imaging the micrometric detection areas of LOCs in contact with intact phone cameras is central to provide such capability. This work demonstrates a disposable and morphing liquid lens concept that can be integrated in LOC devices and refocuses micrometric features in the range necessary for LOC evaluati...

  2. Chip integrated fuel cell accumulator

    Frank, M.; Erdler, G.; Frerichs, H.-P.; Müller, C.; Reinecke, H.

    A unique new design of a chip integrated fuel cell accumulator is presented. The system combines an electrolyser and a self-breathing polymer electrolyte membrane (PEM) fuel cell with integrated palladium hydrogen storage on a silicon substrate. Outstanding advantages of this assembly are the fuel cell with integrated hydrogen storage, the possibility of refuelling it by electrolysis and the opportunity of simply refilling the electrolyte by adding water. By applying an electrical current, wiring the palladium hydrogen storage as cathode and the counter-electrode as anode, the electrolyser produces hydrogen at the palladium surface and oxygen at the electrolyser cell anode. The generated hydrogen is absorbed by the palladium electrode and the hydrogen storage is refilled consequently enabling the fuel cell to function.

  3. Chip integrated fuel cell accumulator

    Frank, M.; Mueller, C.; Reinecke, H. [Laboratory for Process Technology, IMTEK-Department of Microsystems Engineering, University of Freiburg, Georges-Koehler-Allee 103, 79110 Freiburg (Germany); Erdler, G.; Frerichs, H.-P. [Micronas GmbH, Hans-Bunte-Strasse 19, Freiburg (Germany)


    A unique new design of a chip integrated fuel cell accumulator is presented. The system combines an electrolyser and a self-breathing polymer electrolyte membrane (PEM) fuel cell with integrated palladium hydrogen storage on a silicon substrate. Outstanding advantages of this assembly are the fuel cell with integrated hydrogen storage, the possibility of refuelling it by electrolysis and the opportunity of simply refilling the electrolyte by adding water. By applying an electrical current, wiring the palladium hydrogen storage as cathode and the counter-electrode as anode, the electrolyser produces hydrogen at the palladium surface and oxygen at the electrolyser cell anode. The generated hydrogen is absorbed by the palladium electrode and the hydrogen storage is refilled consequently enabling the fuel cell to function. (author)



    According to the relationship of wavelet transform and perfect reconstructive FIR filter banks, this paper presents a real-time chip with adaptive Donoho's non-linear soft-threshold for denoising in different levels of multi-scale space through rearranging the input data during convolving, filtering and sub-sampling.And more important, it gives a simple iterative algorithm to calculate the variance of the noise in interregna with no signal.It works well whether the signal or noise is stationary or not.

  5. Chip based electroanalytical systems for cell analysis

    Spegel, C.; Heiskanen, A.; Skjolding, L.H.D.;


    ' measurements of processes related to living cells, i.e., systems without lysing the cells. The focus is on chip based amperometric and impedimetric cell analysis systems where measurements utilizing solely carbon fiber microelectrodes (CFME) and other nonchip electrode formats, such as CFME for exocytosis......This review with 239 references has as its aim to give the reader an introduction to the kinds of methods used for developing microchip based electrode systems as well as to cover the existing literature on electroanalytical systems where microchips play a crucial role for 'nondestructive...... studies and scanning electrochemical microscopy (SECM) studies of living cells have been omitted. Included is also a discussion about some future and emerging nano tools and considerations that might have an impact on the future of "nondestructive" chip based electroanalysis of living cells....

  6. Perfusion based cell culture chips

    Heiskanen, Arto; Emnéus, Jenny; Dufva, Martin


    Performing cell culture in miniaturized perfusion chambers gives possibilities to experiment with cells under near in vivo like conditions. In contrast to traditional batch cultures, miniaturized perfusion systems provide precise control of medium composition, long term unattended cultures and ti...

  7. Micro-fluidic chip for cell sorting

    Šerý, Mojmír; Pilát, Zdeněk; Ježek, Jan; Kaňka, Jan; Zemánek, Pavel

    Munich : EOS, 2015. ISBN 978-952-93-5069-8. [EOS Conferences at the World of Photonics Congress 2015. Munich (DE), 22.06.2015-25.06.2015] R&D Projects: GA MŠk(CZ) LD14069; GA MŠk(CZ) LO1212; GA TA ČR TA03010642; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : Micro-fluidic chip * cell sorting Subject RIV: BH - Optics, Masers, Lasers

  8. Adaptive Multiclient Network-on-Chip Memory Core: Hardware Architecture, Software Abstraction Layer, and Application Exploration

    Diana Göhringer; Lukas Meder; Stephan Werner; Oliver Oey; Jürgen Becker; Michael Hübner


    This paper presents the hardware architecture and the software abstraction layer of an adaptive multiclient Network-on-Chip (NoC) memory core. The memory core supports the flexibility of a heterogeneous FPGA-based runtime adaptive multiprocessor system called RAMPSoC. The processing elements, also called clients, can access the memory core via the Network-on-Chip (NoC). The memory core supports a dynamic mapping of an address space for the different clients as well as different data transfer ...

  9. 3D-SoftChip: A Novel Architecture for Next-Generation Adaptive Computing Systems

    Lee Mike Myung-Ok


    Full Text Available This paper introduces a novel architecture for next-generation adaptive computing systems, which we term 3D-SoftChip. The 3D-SoftChip is a 3-dimensional (3D vertically integrated adaptive computing system combining state-of-the-art processing and 3D interconnection technology. It comprises the vertical integration of two chips (a configurable array processor and an intelligent configurable switch through an indium bump interconnection array (IBIA. The configurable array processor (CAP is an array of heterogeneous processing elements (PEs, while the intelligent configurable switch (ICS comprises a switch block, 32-bit dedicated RISC processor for control, on-chip program/data memory, data frame buffer, along with a direct memory access (DMA controller. This paper introduces the novel 3D-SoftChip architecture for real-time communication and multimedia signal processing as a next-generation computing system. The paper further describes the advanced HW/SW codesign and verification methodology, including high-level system modeling of the 3D-SoftChip using SystemC, being used to determine the optimum hardware specification in the early design stage.

  10. Adaptive WTA with an analog VLSI neuromorphic learning chip.

    Häfliger, Philipp


    In this paper, we demonstrate how a particular spike-based learning rule (where exact temporal relations between input and output spikes of a spiking model neuron determine the changes of the synaptic weights) can be tuned to express rate-based classical Hebbian learning behavior (where the average input and output spike rates are sufficient to describe the synaptic changes). This shift in behavior is controlled by the input statistic and by a single time constant. The learning rule has been implemented in a neuromorphic very large scale integration (VLSI) chip as part of a neurally inspired spike signal image processing system. The latter is the result of the European Union research project Convolution AER Vision Architecture for Real-Time (CAVIAR). Since it is implemented as a spike-based learning rule (which is most convenient in the overall spike-based system), even if it is tuned to show rate behavior, no explicit long-term average signals are computed on the chip. We show the rule's rate-based Hebbian learning ability in a classification task in both simulation and chip experiment, first with artificial stimuli and then with sensor input from the CAVIAR system. PMID:17385639

  11. On-chip Magnetic Separation and Cell Encapsulation in Droplets

    Chen, A.; Byvank, T.; Bharde, A.; Miller, B. L.; Chalmers, J. J.; Sooryakumar, R.; Chang, W.-J.; Bashir, R.


    The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment could prevent cross-contamination, provide high recovery yield and ability to study biological traits at a single cell level These advantages of on-chip biological experiments contrast to conventional methods, which require bulk samples that provide only averaged information on cell metabolism. We report on a device that integrates microfluidic technology with a magnetic tweezers array to combine the functionality of separation and encapsulation of objects such as immunomagnetically labeled cells or magnetic beads into pico-liter droplets on the same chip. The ability to control the separation throughput that is independent of the hydrodynamic droplet generation rate allows the encapsulation efficiency to be optimized. The device can potentially be integrated with on-chip labeling and/or bio-detection to become a powerful single-cell analysis device.

  12. Real-Time Very Large-Scale Integration Recognition System with an On-Chip Adaptive K-Means Learning Algorithm

    Hou, Zuoxun; Ma, Yitao; Zhu, Hongbo; Zheng, Nanning; Shibata, Tadashi


    A very large-scale integration (VLSI) recognition system equipped with an on-chip learning capability has been developed for real-time processing applications. This system can work in two functional modes of operation: adaptive K-means learning mode and recognition mode. In the adaptive K-means learning mode, the variance ratio criterion (VRC) has been employed to evaluate the quality of K-means classification results, and the evaluation algorithm has been implemented on the chip. As a result, it has become possible for the system to autonomously determine the optimum number of clusters (K). In the recognition mode, the nearest-neighbor search algorithm is very efficiently carried out by the fully parallel architecture employed in the chip. In both modes of operation, many hardware resources are shared and the functionality is flexibly altered by the system controller designed as a finite-state machine (FSM). The chip is implemented on Altera Cyclone II FPGA with 46K logic cells. Its operating clock is 25 MHz and the processing times for adaptive learning and recognition with 256 64-dimension feature vectors are about 0.42 ms and 4 µs, respectively. Both adaptive K-means learning and recognition functions have been verified by experiments using the image data from the COIL-100 (Columbia University Object Image Library) database.

  13. An OCP Compliant Network Adapter for GALS-based SoC Design Using the MANGO Network-on-Chip

    Bjerregaard, Tobias; Mahadevan, Shankar; Olsen, Rasmus Grøndahl;


    The demand for IP reuse and system level scalability in System-on-Chip (SoC) designs is growing. Network-onchip (NoC) constitutes a viable solution space to emerging SoC design challenges. In this paper we describe an OCP compliant network adapter (NA) architecture for the MANGO NoC. The NA...... decouples communication and computation, providing memory-mapped OCP transactions based on primitive message-passing services of the network. Also, it facilitates GALS-type systems, by adapting to the clockless network. This helps leverage a modular SoC design flow. We evaluate performance and cost of 0.......13 um CMOS standard cell instantiations of the architecture....

  14. Neural Cell Chip Based Electrochemical Detection of Nanotoxicity

    Md. Abdul Kafi


    Full Text Available Development of a rapid, sensitive and cost-effective method for toxicity assessment of commonly used nanoparticles is urgently needed for the sustainable development of nanotechnology. A neural cell with high sensitivity and conductivity has become a potential candidate for a cell chip to investigate toxicity of environmental influences. A neural cell immobilized on a conductive surface has become a potential tool for the assessment of nanotoxicity based on electrochemical methods. The effective electrochemical monitoring largely depends on the adequate attachment of a neural cell on the chip surfaces. Recently, establishment of integrin receptor specific ligand molecules arginine-glycine-aspartic acid (RGD or its several modifications RGD-Multi Armed Peptide terminated with cysteine (RGD-MAP-C, C(RGD4 ensure farm attachment of neural cell on the electrode surfaces either in their two dimensional (dot or three dimensional (rod or pillar like nano-scale arrangement. A three dimensional RGD modified electrode surface has been proven to be more suitable for cell adhesion, proliferation, differentiation as well as electrochemical measurement. This review discusses fabrication as well as electrochemical measurements of neural cell chip with particular emphasis on their use for nanotoxicity assessments sequentially since inception to date. Successful monitoring of quantum dot (QD, graphene oxide (GO and cosmetic compound toxicity using the newly developed neural cell chip were discussed here as a case study. This review recommended that a neural cell chip established on a nanostructured ligand modified conductive surface can be a potential tool for the toxicity assessments of newly developed nanomaterials prior to their use on biology or biomedical technologies.

  15. Microfluidic cell chips for high-throughput drug screening.

    Chi, Chun-Wei; Ahmed, Ah Rezwanuddin; Dereli-Korkut, Zeynep; Wang, Sihong


    The current state of screening methods for drug discovery is still riddled with several inefficiencies. Although some widely used high-throughput screening platforms may enhance the drug screening process, their cost and oversimplification of cell-drug interactions pose a translational difficulty. Microfluidic cell-chips resolve many issues found in conventional HTS technology, providing benefits such as reduced sample quantity and integration of 3D cell culture physically more representative of the physiological/pathological microenvironment. In this review, we introduce the advantages of microfluidic devices in drug screening, and outline the critical factors which influence device design, highlighting recent innovations and advances in the field including a summary of commercialization efforts on microfluidic cell chips. Future perspectives of microfluidic cell devices are also provided based on considerations of present technological limitations and translational barriers. PMID:27071838

  16. Accurate detection of carcinoma cells by use of a cell microarray chip.

    Shohei Yamamura

    Full Text Available BACKGROUND: Accurate detection and analysis of circulating tumor cells plays an important role in the diagnosis and treatment of metastatic cancer treatment. METHODS AND FINDINGS: A cell microarray chip was used to detect spiked carcinoma cells among leukocytes. The chip, with 20,944 microchambers (105 µm width and 50 µm depth, was made from polystyrene; and the formation of monolayers of leukocytes in the microchambers was observed. Cultured human T lymphoblastoid leukemia (CCRF-CEM cells were used to examine the potential of the cell microarray chip for the detection of spiked carcinoma cells. A T lymphoblastoid leukemia suspension was dispersed on the chip surface, followed by 15 min standing to allow the leukocytes to settle down into the microchambers. Approximately 29 leukocytes were found in each microchamber when about 600,000 leukocytes in total were dispersed onto a cell microarray chip. Similarly, when leukocytes isolated from human whole blood were used, approximately 89 leukocytes entered each microchamber when about 1,800,000 leukocytes in total were placed onto the cell microarray chip. After washing the chip surface, PE-labeled anti-cytokeratin monoclonal antibody and APC-labeled anti-CD326 (EpCAM monoclonal antibody solution were dispersed onto the chip surface and allowed to react for 15 min; and then a microarray scanner was employed to detect any fluorescence-positive cells within 20 min. In the experiments using spiked carcinoma cells (NCI-H1650, 0.01 to 0.0001%, accurate detection of carcinoma cells was achieved with PE-labeled anti-cytokeratin monoclonal antibody. Furthermore, verification of carcinoma cells in the microchambers was performed by double staining with the above monoclonal antibodies. CONCLUSION: The potential application of the cell microarray chip for the detection of CTCs was shown, thus demonstrating accurate detection by double staining for cytokeratin and EpCAM at the single carcinoma cell level.

  17. Single cancer cell analysis on a chip

    Yang, Yoonsun


    Cancer cells in blood may represent “a real time liquid biopsy” through the interrogation of single cancer cells thereby determining the outspread of their heterogeneity and guiding therapy. In this thesis, we focused on single cancer cell analysis downstream of the isolation of cancer cells from blood. We designed and developed various microfluidic devices for genetic and phenotypic characterization of single cancer cells. The limited DNA content in a single cell requires DNA amplification t...

  18. Single cell enzyme diagnosis on the chip

    Jensen, Sissel Juul; Harmsen, Charlotte; Nielsen, Mette Juul;


    Conventional diagnosis based on ensemble measurements often overlooks the variation among cells. Here, we present a droplet-microfluidics based platform to investigate single cell activities. Adopting a previously developed isothermal rolling circle amplification-based assay, we demonstrate detec...

  19. Thermometry in dielectrophoresis chips for contact-free cell handling

    Cell biology applications, protocols in immunology and stem cell research, require that individual cells are handled under strict control of their contacts to other cells or synthetic surfaces. Dielectrophoresis (DEP) in microfluidic chips is an established technique to investigate, group, wash, cultivate and sort cells contact-free under physiological conditions: microelectrode octode cages, versatile dielectrophoretic elements energized with radio frequency electric fields, stably trap single cells or cellular aggregates. For medical applications and cell cultivation, possible side effects of the dielectrophoretic manipulation, such as membrane polarization and Joule heating, have to be quantified. Therefore, we characterized the electric field-induced warming in dielectrophoretic cages using ohmic resistance measurements, fluorometry, liquid crystal beads, infra-red thermography and bubble size thermometry. We compare the results of these techniques with respect to the influences of voltage, electric conductivity of buffer, frequency, cage size and electrode surface. We conclude that in the culture medium thermal effects may be neglected if low voltages and an electric field-reducing phase pattern are used. Our experimental results provide explicit values for estimating the thermal effect on dielectrophoretically caged cells and show that Joule heating is best minimized by optimizing the cage geometry and reducing the buffer conductivity. The results may additionally serve to evaluate and improve theoretical predictions on field-induced effects. Based on present-day chip processing possibilities, DEP is well suited for the manipulation of cells

  20. A self-adaptive full asynchronous bi-directional transmission channel for network-on-chips

    To improve two shortcomings of conventional network-on-chips, i.e. low utilization rate in channels between routers and excessive interconnection lines, this paper proposes a full asynchronous self-adaptive bi-directional transmission channel. It can utilize interconnection lines and register resources with high efficiency, and dynamically detect the data transmission state between routers through a direction regulator, which controls the sequencer to automatically adjust the transmission direction of the bi-directional channel, so as to provide a flexible data transmission environment. Null convention logic units are used to make the circuit quasi-delay insensitive and highly robust. The proposed bi-directional transmission channel is implemented based on SMIC 0.18 μm standard CMOS technology. Post-layout simulation results demonstrate that this self-adaptive bi-directional channel has better performance on throughput, transmission flexibility and channel bandwidth utilization compared to a conventional single direction channel. Moreover, the proposed channel can save interconnection lines up to 30% and can provide twice the bandwidth resources of a single direction transmission channel. The proposed channel can apply to an on-chip network which has limited resources of registers and interconnection lines. (semiconductor integrated circuits)

  1. Microfluidic-chip platform for cell sorting

    Malik, Sarul; Balyan, Prerna; Akhtar, J.; Agarwal, Ajay


    Cell sorting and separation are considered to be very crucial preparatory steps for numerous clinical diagnostics and therapeutics applications in cell biology research arena. Label free cell separation techniques acceptance rate has been increased to multifold by various research groups. Size based cell separation method focuses on the intrinsic properties of the cell which not only avoids clogging issues associated with mechanical and centrifugation filtration methods but also reduces the overall cost for the process. Consequentially flow based cell separation method for continuous flow has attracted the attention of millions. Due to the realization of structures close to particle size in micro dimensions, the microfluidic devices offer precise and rapid particle manipulation which ultimately leads to an extraordinary cell separation results. The proposed microfluidic device is fabricated to separate polystyrene beads of size 1 µm, 5 µm, 10 µm and 20 µm. The actual dimensions of blood corpuscles were kept in mind while deciding the particle size of polystyrene beads which are used as a model particles for study.

  2. Self-Adaptive On-Chip System Based on Cross-Layer Adaptation Approach

    Kais Loukil


    Full Text Available The emergence of mobile and battery operated multimedia systems and the diversity of supported applications mount new challenges in terms of design efficiency of these systems which must provide a maximum application quality of service (QoS in the presence of a dynamically varying environment. These optimization problems cannot be entirely solved at design time and some efficiency gains can be obtained at run-time by means of self-adaptivity. In this paper, we propose a new cross-layer hardware (HW/software (SW adaptation solution for embedded mobile systems. It supports application QoS under real-time and lifetime constraints via coordinated adaptation in the hardware, operating system (OS, and application layers. Our method relies on an original middleware solution used on both global and local managers. The global manager (GM handles large, long-term variations whereas the local manager (LM is used to guarantee real-time constraints. The GM acts in three layers whereas the LM acts in application and OS layers only. The main role of GM is to select the best configuration for each application to meet the constraints of the system and respect the preferences of the user. The proposed approach has been applied to a 3D graphics application and successfully implemented on an Altera FPGA.

  3. Automated, Miniaturized and Integrated Quality Control-on-Chip (QC-on-a-Chip) for Advanced Cell Therapy Applications

    Wartmann, David; Rothbauer, Mario; Kuten, Olga; Barresi, Caterina; Visus, Carmen; Felzmann, Thomas; Ertl, Peter


    The combination of microfabrication-based technologies with cell biology has laid the foundation for the development of advanced in vitro diagnostic systems capable of evaluating cell cultures under defined, reproducible and standardizable measurement conditions. In the present review we describe recent lab-on-a-chip developments for cell analysis and how these methodologies could improve standard quality control in the field of manufacturing cell-based vaccines for clinical purposes. We highlight in particular the regulatory requirements for advanced cell therapy applications using as an example dendritic cell-based cancer vaccines to describe the tangible advantages of microfluidic devices that overcome most of the challenges associated with automation, miniaturization and integration of cell-based assays. As its main advantage lab-on-a-chip technology allows for precise regulation of culturing conditions, while simultaneously monitoring cell relevant parameters using embedded sensory systems. State-of-the-art lab-on-a-chip platforms for in vitro assessment of cell cultures and their potential future applications for cell therapies and cancer immunotherapy are discussed in the present review.

  4. Semiconductor chips with ion channels, nerve cells and brain

    Fromherz, Peter


    The electrical interfacing of individual nerve cells and semiconductor microstructures as well as the assembly of neuronal networks and microelectronic circuits, is considered. At first the planar core-coat conductor of a neuron-silicon junction is studied as it determines the coupling of ion-conducting neurons and electron-conducting silicon. The width of the cleft between cell and chip, the resistance of cleft and voltage-gate ion channels in the junction are investigated. On that basis, a subsequent section describes the electronic interfacing of individual cultured neurons with silicon microstructures as well as the integration of microelectronics with small neuronal networks grown in culture. In a final part, the electronic interfacing of cultured brain slices is addressed. The goal of this approach is an integration of neuronal network dynamics and digital computation on a microscopic level for studies in brain research, biosensorics, information technology and medical prosthetics.

  5. Adaptive Multi-Dimensional Particle In Cell

    Lapenta, Giovanni


    Kinetic Particle In Cell (PIC) methods can extend greatly their range of applicability if implicit time differencing and spatial adaption are used to address the wide range of time and length scales typical of plasmas. For implicit differencing, we refer the reader to our recent summary of the implicit moment PIC method implemented in our CELESTE3D code [G. Lapenta, Phys. Plasmas, 13, 055904 (2006)]. Instead, the present document deals with the issue of PIC spatial adaptation. Adapting a kine...

  6. On-chip cell sorting via patterned magnetic traps

    Byvank, Tom; Prikockis, Michael; Chen, Aaron; Miller, Brandon; Chalmers, Jeffrey; Sooryakumar, Ratnasingham


    Due to their importance in research for the diagnosis and treatment of cancer, numerous schemes have been developed to sort rare cell populations, e.g., circulating tumor cells (CTCs), from a larger ensemble of cells. Here, we improve upon a previously developed microfluidic device (Lab Chip 13, 1172, (2013)) to increase throughput and sorting purity of magnetically labeled cells. The separation mechanism involves controlling magnetic forces by manipulating the magnetic domain structures of embedded permalloy microdisks with weak external fields. These forces move labeled cells from the input flow stream into an adjacent buffer flow stream. Such magnetically activated transfer separates the magnetic entities from their non-magnetic counterparts as the two flow streams split apart and move toward their respective outputs. Purity of the magnetic output is modulated by the withdrawal rate of the non-magnetic output relative to the inputs. A proof of concept shows that CTCs from metastatic breast cancer patients can be sorted, recovered from the device, and confirmed as CTCs using separate immunofluorescence staining and analysis. With further optimizations, the channel could become a useful device for high purity final sorting of enriched patient cell samples.

  7. Dynamical Adaptation in Terrorist Cells/Networks

    Hussain, Dil Muhammad Akbar; Ahmed, Zaki


    followers etc. In this research we analyze and predict the most likely role a particular node can adapt once a member of the network is either killed or caught. The adaptation is based on computing Bayes posteriori probability of each node and the level of the said node in the network structure.......Typical terrorist cells/networks have dynamical structure as they evolve or adapt to changes which may occur due to capturing or killing of a member of the cell/network. Analytical measures in graph theory like degree centrality, betweenness and closeness centralities are very common and have long...

  8. Hybrid Adaptive Routing in Network-on-chips Using KLSA with Dijkstra Algorithm

    M. Muthulakshmi


    Full Text Available The aim of this study is to analyse dynamic programming in large scale, complex networks is more important in the fields of scientific and engineering. Recent applications needs the analysis of scale-free networks with many millions of nodes and edges; presenting a huge computational challenge. Employing distributed networks on-chip infrastructure presents a unique opportunity of delivering power efficient and massive parallel accelerations. Dynamic Programming (DP network is a massive parallel and high throughput network architecture, which provides real-time computation for shortest path problems. This network combines with the NoC to enable optimal traffic control based on the online network status and, provides optimal path planning and dynamic routing with proposed novel routing mechanics heuristic K-Step Look Ahead (KLSA in deadlock free architecture. K-step look ahead routing algorithm based calculating the Manhattan distance has some disadvantages and it affects the overall performance of the routing algorithm. In order to overcome aforementioned disadvantages of manhattan distance and improving the efficiency of K-step looks ahead algorithm proposing a dijkstra algorithm for calculating the distance between two nodes. Here in implementation, the results are compared with existing routing schemas or algorithms like XY, DyAD, odd-even, odd-even routing with an NoP selection scheme. The DP network presents a simple, reliable and efficient methodology to enable adaptive routing in NoCs.

  9. 'Fluorescent Cell Chip' for immunotoxicity testing: Development of the c-fos expression reporter cell lines

    The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals

  10. Hybrid cell sorters for on-chip cell separation by hydrodynamics and magnetophoresis

    The classification of cells is important for medical diagnosis and medicine research. A micro-scale analysis system for blood allows immediate diagnosis, regardless of time or location. Rapid handling of biological cells is required for the development of lab-on-a-chip and point-of-care technologies. In previous papers, the reported sample solution flow rates for hydrodynamic cell separation ranged from 0.1 to tens of μl min−1. This paper proposes a hybrid cell sorter that combines hydrodynamics and magnetophoresis. This cell sorter is proposed for improving the classification efficiency of a virtual impactor-based cell sorter and for permitting the hydrodynamic cell separation with high throughput. In addition, its performance has been evaluated in the classification of Jurkat cells and blood cells. In the Jurkat cell experiment, the classification efficiency of Jurkat cells at the major outlet decreased from 70 to 50.8% with the proposed hybrid scheme. The flow rate for cell separation was 1 ml min−1. The classification efficiency of red blood cells (RBCs) increased from 75.2 to 86.8% with the application of a magnetic field. Also, the classification efficiency of white blood cells (WBCs) decreased from 83.8 to 70.9% with an applied magnetic field. Experimental results demonstrated that the classification efficiency of blood cells can be modulated and enhanced by magnetophoresis and that the hybrid cell sorter has potential for lab-on-a-chip applications.

  11. Transparent polymeric cell culture chip with integrated temperature control and uniform media perfusion

    Petronis, Sarunas; Stangegaard, Michael; Christensen, C.;


    Modern microfabrication and microfluidic technologies offer new opportunities in the design and fabrication of miniaturized cell culture systems for online monitoring of living cells. We used laser micromachining and thermal bonding to fabricate an optically transparent, low-cost polymeric chip for...... long-term online cell culture observation under controlled conditions. The chip incorporated a microfluidic flow equalization system, assuring uniform perfusion of the cell culture media throughout the cell culture chamber. The integrated indium-tin-oxide heater and miniature temperature probe linked...... to an electronic feedback system created steady and spatially uniform thermal conditions with minimal interference to the optical transparency of the chip. The fluidic and thermal performance of the chip was verified by finite element modeling and by operation tests under fluctuating ambient...

  12. Numerical simulation of isolation of cancer cells in a microfluidic chip

    Djukic, T.; Topalovic, M.; Filipovic, N.


    Cancer is a disease that is characterized by the uncontrolled increase of numbers of cells. Circulating tumour cells (CTCs) are separated from the primary tumor, circulate in the bloodstream and form metastases. Circulating tumor cells can be identified in the blood of a patient by taking a blood sample. Microfluidic chips are a new technique that is used to isolate these cells from the blood sample. In this paper a numerical model is presented that is able to simulate the motion of individual cells through a microfluidic chip. The proposed numerical model gives very valuable insight into the processes happening within a microfluidic chip. The accuracy of the proposed model is compared with experimental results. The experimental setup that is described in literature is used to create identical geometrical domains and define simulation parameters. A good agreement of experimental and numerical results demonstrates that the proposed model can be successfully used to simulate complex behaviour of CTCs inside microfluidic chips.

  13. On-chip lysis of mammalian cells through a handheld corona device.

    Escobedo, C; Bürgel, S C; Kemmerling, S; Sauter, N; Braun, T; Hierlemann, A


    On-chip lysis is required in many lab-on-chip applications involving cell studies. In these applications, the complete disruption of the cellular membrane and a high lysis yield is essential. Here, we present a novel approach to lyse cells on-chip through the application of electric discharges from a corona handheld device. The method only requires a microfluidic chip and a low-cost corona device. We demonstrate the effective lysis of BHK and eGFP HCT 116 cells in the sub-second time range using an embedded microelectrode. We also show cell lysis of non-adherent K562 leukemia cells without the use of an electrode in the chip. Cell lysis has been assessed through the use of bright-field microscopy, high-speed imaging and cell-viability fluorescence probes. The experimental results show effective cell lysis without any bubble formation or significant heating. Due to the simplicity of both the components involved and the lysis procedure, this technique offers an inexpensive lysis option with the potential for integration into lab-on-a-chip devices. PMID:26055165

  14. Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

    Liang Huang


    Full Text Available Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.

  15. Lab-on-chip platform for circulating tumor cells isolation

    Maurya, D. K.; Fooladvand, M.; Gray, E.; Ziman, M.; Alameh, K.


    We design, develop and demonstrate the principle of a continuous, non-intrusive, low power microfluidics-based lab-ona- chip (LOC) structure for Circulating Tumor Cell (CTC) separation. Cell separation is achieved through 80 cascaded contraction and expansion microchannels of widths 60 μm and 300 μm, respectively, and depth 60 μm, which enable momentum-change-induced inertial forces to be exerted on the cells, thus routing them to desired destinations. The total length of the developed LOC is 72 mm. The LOC structure is simulated using the COMSOL multiphysics software, which enables the optimization of the dimensions of the various components of the LOC structure, namely the three inlets, three filters, three contraction and expansion microchannel segments and five outlets. Simulation results show that the LOC can isolate CTCs of sizes ranging from 15 to 30 μm with a recovery rate in excess of 90%. Fluorescent microparticles of two different sizes (5 μm and 15 μm), emulating blood and CTC cells, respectively, are used to demonstrate the principle of the developed LOC. A mixture of these microparticles is injected into the primary LOC inlet via an electronically-controlled syringe pump, and the large-size particles are routed to the primary LOC outlet through the contraction and expansion microchannels. Experimental results demonstrate the ability of the developed LOC to isolate particles by size exclusion with an accuracy of 80%. Ongoing research is focusing on the LOC design improvement for better separation efficiency and testing of biological samples for isolation of CTCs.

  16. Regulated cell death and adaptive stress responses.

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kepp, Oliver; Kroemer, Guido


    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID:27048813

  17. Detection of immunotoxicity using T-cell based cytokine reporter cell lines ('Cell Chip')

    Safety assessment of chemicals and drugs is an important regulatory issue. The evaluation of potential adverse effects of compounds on the immune system depends today on animal experiments. An increasing demand, however, exists for in vitro alternatives. Cytokine measurement is a promising tool to evaluate chemical exposure effects on the immune system. Fortunately, this type of measurement can be performed in conjunction with in vitro exposure models. We have taken these considerations as the starting point to develop an in vitro method to efficiently screen compounds for potential immunotoxicity. The T-cell lymphoma cell line EL-4 was transfected with the regulatory sequences of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-γ or actin fused to the gene for enhanced green fluorescent protein (EGFP) in either a stabile or a destabilised form. Consequently, changes in fluorescence intensity represent changes in cytokine expression with one cell line per cytokine. We used this prototype 'Cell Chip' to test, by means of flow cytometry, the immunomodulatory potential of 13 substances and were able to detect changes in cytokine expression in 12 cases (successful for cyclosporine, rapamycin, pentamidine, thalidomide, bis(tri-n-butyltin)oxide, house dust mite allergen (Der p I), 1-chloro-2,4-dinitrobenzene, benzocaine, tolylene 2,4-diisocyanate, potassium tetrachloroplatinate, sodium dodecyl sulphate and mercuric chloride; unsuccessful for penicillin G). In conclusion, this approach seems promising for in vitro screening for potential immunotoxicity, especially when additional cell lines besides T-cells are included

  18. Adaptive Multi-Dimensional Particle In Cell

    Lapenta, Giovanni


    Kinetic Particle In Cell (PIC) methods can extend greatly their range of applicability if implicit time differencing and spatial adaption are used to address the wide range of time and length scales typical of plasmas. For implicit differencing, we refer the reader to our recent summary of the implicit moment PIC method implemented in our CELESTE3D code [G. Lapenta, Phys. Plasmas, 13, 055904 (2006)]. Instead, the present document deals with the issue of PIC spatial adaptation. Adapting a kinetic PIC code requires two tasks: adapting the grid description of the fields and moments and adapting the particle description of the distribution function. Below we address both issues. First, we describe how grid adaptation can be guided by appropriate measures of the local accuracy of the solution. Based on such information, grid adaptation can be obtained by moving grid points from regions of lesser interest to regions of higher interest or by adding and removing points. We discuss both strategies. Second, we describe...

  19. Designing a WISHBONE Protocol Network Adapter for an Asynchronous Network-on-Chip

    Soliman, Ahmed H. M.; E. M.Saad; M El Bably; Keshk, Hesham M. A. M.


    The Scaling of microchip technologies, from micron to submicron and now to deep sub-micron (DSM) range, has enabled large scale systems-on-chip (SoC). In future deep submicron (DSM) designs, the interconnect effect will definitely dominate performance. Network-on-Chip (NoC) has become a promising solution to bus-based communication infrastructure limitations. NoC designs usually targets Application Specific Integrated Circuits (ASICs), however, the fabrication process costs a lot. Implementin...

  20. Joining microelectronics and microionics: Nerve cells and brain tissue on semiconductor chips

    Fromherz, Peter


    The direct electrical interfacing of semiconductor chips with individual nerve cells and with brain tissue is considered. At first, the structure of the cell-chip contact is described and then the electrical coupling is characterized between ion channels, the electrical elements of nerve cells, and transistors and capacitors of silicon chips. On that basis, the signal transmission between microelectronics and microionics is implemented in both directions. Simple hybrid systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue on silicon. The application of CMOS chips with capacitively coupled recording sites allows an imaging of neuronal activity with high spatiotemporal resolution. Goal of the work is an integration of neuronal network dynamics and digital electronics on a microscopic level for applications in brain research, medical prosthetics and information technology.

  1. CHIP mediates down-regulation of nucleobindin-1 in preosteoblast cell line models.

    Xue, Fuying; Wu, Yanping; Zhao, Xinghui; Zhao, Taoran; Meng, Ying; Zhao, Zhanzhong; Guo, Junwei; Chen, Wei


    Nucleobindin-1 (NUCB1), also known as Calnuc, is a highly conserved, multifunctional protein widely expressed in tissues and cells. It contains two EF-hand motifs which have been shown to play a crucial role in binding Ca(2+) ions. In this study, we applied comparative two-dimensional gel electrophoresis to characterize differentially expressed proteins in HA-CHIP over-expressed and endogenous CHIP depleted MC3T3-E1 stable cell lines, identifying NUCB1 as a novel CHIP/Stub1 targeted protein. NUCB1 interacts with and is down-regulated by CHIP by both proteasomal dependent and independent pathways, suggesting that CHIP-mediated down-regulation of nucleobindin-1 might play a role in osteoblast differentiation. The chaperone protein Hsp70 was found to be important for CHIP and NUCB1 interaction as well as CHIP-mediated NUCB1 down-regulation. Our findings provide new insights into understanding the stability regulation of NUCB1. PMID:27178152

  2. Research on Electric Impedance Spectroscopy of Living Cell Suspensions by a Chip with Microelectrodes

    Xing Yang; Zhaoying Zhou; Mingfei Xiao; Ying Wu; Shangfeng Liu


    A microfabricated electrical impedance spectroscopy (EIS) chip with microelectrodes was developed. The substrate and the electrodes of the chip were made of glass and gold, respectively. The experimental results demonstrated that the EIS-chip could distinguish different solutions (physiological saline, culture medium, living cell suspension etc.) by scanning from 10Hz to 45kHz. A 6-element circuit model was used for fitting the real part and the imaginary part admittance curves of the living cell suspension. An actual circuit was also built and tested to verify the 6-element circuit model proposed. The micro-EIS chip has several advantages including the use of small sample volumes, high resolution and ease of operation. It shows good application prospects in the areas of cellular electrophysiology, drug screening and bio-sensors etc.

  3. Universal lab-on-a-chip platform for complex, perfused 3D cell cultures

    Sonntag, F.; Schmieder, F.; Ströbel, J.; Grünzner, S.; Busek, M.; Günther, K.; Steege, T.; Polk, C.; Klotzbach, U.


    The miniaturization, rapid prototyping and automation of lab-on-a-chip technology play nowadays a very important role. Lab-on-a-chip technology is successfully implemented not only for environmental analysis and medical diagnostics, but also as replacement of animals used for the testing of substances in the pharmaceutical and cosmetics industries. For that purpose the Fraunhofer IWS and partners developed a lab-on-a-chip platform for perfused cell-based assays in the last years, which includes different micropumps, valves, channels, reservoirs and customized cell culture modules. This technology is already implemented for the characterization of different human cell cultures and organoids, like skin, liver, endothelium, hair follicle and nephron. The advanced universal lab-on-a-chip platform for complex, perfused 3D cell cultures is divided into a multilayer basic chip with integrated micropump and application-specific 3D printed cell culture modules. Moreover a technology for surface modification of the printed cell culture modules by laser micro structuring and a complex and flexibly programmable controlling device based on an embedded Linux system was developed. A universal lab-on-a-chip platform with an optional oxygenator and a cell culture module for cubic scaffolds as well as first cell culture experiments within the cell culture device will be presented. The module is designed for direct interaction with robotic dispenser systems. This offers the opportunity to combine direct organ printing of cells and scaffolds with the microfluidic cell culture module. The characterization of the developed system was done by means of Micro-Particle Image Velocimetry (μPIV) and an optical oxygen measuring system.

  4. Acoustic micro-vortexing of fluids, particles and cells in disposable microfluidic chips.

    Iranmanesh, Ida; Ohlin, Mathias; Ramachandraiah, Harisha; Ye, Simon; Russom, Aman; Wiklund, Martin


    We demonstrate an acoustic platform for micro-vortexing in disposable polymer microfluidic chips with small-volume (20 μl) reaction chambers. The described method is demonstrated for a variety of standard vortexing functions, including mixing of fluids, re-suspension of a pellet of magnetic beads collected by a magnet placed on the chip, and lysis of cells for DNA extraction. The device is based on a modified Langevin-type ultrasonic transducer with an exponential horn for efficient coupling into the microfluidic chip, which is actuated by a low-cost fixed-frequency electronic driver board. The transducer is optimized by numerical modelling, and different demonstrated vortexing functions are realized by actuating the transducer for varying times; from fractions of a second for fluid mixing, to half a minute for cell lysis and DNA extraction. The platform can be operated during 1 min below physiological temperatures with the help of a PC fan, a Peltier element and an aluminum heat sink acting as the chip holder. As a proof of principle for sample preparation applications, we demonstrate on-chip cell lysis and DNA extraction within 25 s. The method is of interest for automating and chip-integrating sample preparation procedures in various biological assays. PMID:27444649

  5. Multicolor fluorescence microscopic imaging of cancer cells on the plasmonic chip (Presentation Recording)

    Tawa, Keiko; Sasakawa, Chisato; Yamamura, Shohei; Shibata, Izumi; Kataoka, Masatoshi


    A plasmonic chip which is a metal coated substrate with grating structure can provide the enhanced fluorescence by the grating-coupled surface plasmon field. In our previous studies, bright epi-fluorescence microscopic imaging of neuron cells and sensitive immunosesnsing have been reported. In this study, two kinds of breast cancer cells, MCF-7 and MDA-MB231, were observed with epi-fluorescence microscope on the plasmonic chip with 2D hole-arrays . They were multicolor stained with 4', 6-diamidino-2-phenylindole (DAPI) and allophycocyanin (APC)-labeled anti-epithelial cell adhesion molecule (EpCAM) antibody. Our plasmonic chip provided the brighter fluorescence images of these cells compared with the glass slide. Even in the cells including few EpCAM, the distribution of EpCAM was clearly observed in the cell membrane. It was found that the plasmonic chip can be one of the powerful tools to detect the marker protein existing around the chip surface even at low concentration.

  6. On-chip Extraction of Intracellular Molecules in White Blood Cells from Whole Blood

    Choi, Jongchan; Hyun, Ji-Chul; Yang, Sung


    The extraction of virological markers in white blood cells (WBCs) from whole blood—without reagents, electricity, or instruments—is the most important first step for diagnostic testing of infectious diseases in resource-limited settings. Here we develop an integrated microfluidic chip that continuously separates WBCs from whole blood and mechanically ruptures them to extract intracellular proteins and nucleic acids for diagnostic purposes. The integrated chip is assembled with a device that separates WBCs by using differences in blood cell size and a mechanical cell lysis chip with ultra-sharp nanoblade arrays. We demonstrate the performance of the integrated device by quantitatively analyzing the levels of extracted intracellular proteins and genomic DNAs. Our results show that compared with a conventional method, the device yields 120% higher level of total protein amount and similar levels of gDNA (90.3%). To demonstrate its clinical application to human immunodeficiency virus (HIV) diagnostics, the developed chip was used to process blood samples containing HIV-infected cells. Based on PCR results, we demonstrate that the chip can extract HIV proviral DNAs from infected cells with a population as low as 102/μl. These findings suggest that the developed device has potential application in point-of-care testing for infectious diseases in developing countries.

  7. In-chip fabrication of free-form 3D constructs for directed cell migration analysis

    Olsen, Mark Holm; Hjortø, Gertrud Malene; Hansen, Morten;


    Free-form constructs with three-dimensional (3D) microporosity were fabricated by two-photon polymerization inside the closed microchannel of an injection-molded, commercially available polymer chip for analysis of directed cell migration. Acrylate constructs were produced as woodpile topologies...... with a range of pore sizes from 5 × 5 μm to 15 × 15 μm and prefilled with fibrillar collagen. Dendritic cells seeded into the polymer chip in a concentration gradient of the chemoattractant CCL21 efficiently negotiated the microporous maze structure for pore sizes of 8 × 8 μm or larger. The cells...

  8. Injection molded polymer chip for electrochemical and electrophysiological recordings from single cells

    Tanzi, Simone; Larsen, Simon Tylsgaard; Taboryski, Rafael J.

    We present a novel method to fabricate an all in polymer injection molded chip for electrochemical cell recordings and lateral cell trapping. The complete device is molded in thermoplastic polymer and it results from assembling two halves. We tested spin-coated conductive polymer poly(3...

  9. Adaptive Code Division Multiple Access Protocol for Wireless Network-on-Chip Architectures

    Vijayakumaran, Vineeth

    Massive levels of integration following Moore's Law ushered in a paradigm shift in the way on-chip interconnections were designed. With higher and higher number of cores on the same die traditional bus based interconnections are no longer a scalable communication infrastructure. On-chip networks were proposed enabled a scalable plug-and-play mechanism for interconnecting hundreds of cores on the same chip. Wired interconnects between the cores in a traditional Network-on-Chip (NoC) system, becomes a bottleneck with increase in the number of cores thereby increasing the latency and energy to transmit signals over them. Hence, there has been many alternative emerging interconnect technologies proposed, namely, 3D, photonic and multi-band RF interconnects. Although they provide better connectivity, higher speed and higher bandwidth compared to wired interconnects; they also face challenges with heat dissipation and manufacturing difficulties. On-chip wireless interconnects is one other alternative proposed which doesn't need physical interconnection layout as data travels over the wireless medium. They are integrated into a hybrid NOC architecture consisting of both wired and wireless links, which provides higher bandwidth, lower latency, lesser area overhead and reduced energy dissipation in communication. However, as the bandwidth of the wireless channels is limited, an efficient media access control (MAC) scheme is required to enhance the utilization of the available bandwidth. This thesis proposes using a multiple access mechanism such as Code Division Multiple Access (CDMA) to enable multiple transmitter-receiver pairs to send data over the wireless channel simultaneously. It will be shown that such a hybrid wireless NoC with an efficient CDMA based MAC protocol can significantly increase the performance of the system while lowering the energy dissipation in data transfer. In this work it is shown that the wireless NoC with the proposed CDMA based MAC protocol

  10. Plant Cell Adaptive Responses to Microgravity

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    Microgravity is an abnormal environmental condition that plays no role in the functioning of biosphere. Nevertheless, the chronic effect of microgravity in space flight as an unfamiliar factor does not prevent the development of adaptive reactions at the cellular level. In real microgravity in space flight under the more or less optimal conditions for plant growing, namely temperature, humidity, CO2, light intensity and directivity in the hardware angiosperm plants perform an “reproductive imperative”, i.e. they flower, fruit and yield viable seeds. It is known that cells of a multicellular organism not only take part on reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of the identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and subcellular level in real and simulated microgravity is considered. Cytological studies of plants developing in real and simulated microgravity made it possible to establish that the processes of mitosis, cytokinesis, and tissue differentiation of vegetative and generative organs are largely normal. At the same time, under microgravity, essential reconstruction in the structural and functional organization of cell organelles and cytoskeleton, as well as changes in cell metabolism and homeostasis have been described. In addition, new interesting data concerning the influence of altered gravity on lipid peroxidation intensity, the level of reactive oxygen species, and antioxidant system activity, just like on the level of gene expression and synthesis of low-molecular and high-molecular heat shock proteins were recently obtained. So, altered gravity caused time-dependent increasing of the HSP70 and HSP90 levels in cells, that may indicate temporary strengthening of their functional loads that is necessary for re-establish a new cellular homeostasis. Relative qPCR results showed that

  11. Analysis of DNA-chip and antigen-chip data: studies of cancer, stem cells and autoimmune diseases

    Domany, Eytan


    Biology has undergone a revolution during the past decade. Deciphering the human genome has opened new horizons, among which the advent of DNA microarrays has been perhaps the most significant. These miniature measuring devices report the levels at which tens of thousands of genes are expressed in a collection of cells of interest (such as tissue from a tumor). I describe here briefly this technology and present an example of how analysis of data obtained from such high throughput experiments provides insights of possible clinical and therapeutic relevance for Acute Lymphoblastic Leukemia. Next, I describe how gene expression data is used to deduce a new design principle, " Just In Case", used by stem cells. Finally I briefly review a different novel technology, of antigen chips, which provide a fingerprint of a subject's immune system and may become a predictive clinical tool. The work reviewed here was done in collaboration with numerous colleagues and students.

  12. Development of an Integrated Chip for Automatic Tracking and Positioning Manipulation for Single Cell Lysis

    Chao-Wang Young


    Full Text Available This study adopted a microelectromechanical fabrication process to design a chip integrated with electroosmotic flow and dielectrophoresis force for single cell lysis. Human histiocytic lymphoma U937 cells were driven rapidly by electroosmotic flow and precisely moved to a specific area for cell lysis. By varying the frequency of AC power, 15 V AC at 1 MHz of frequency configuration achieved 100% cell lysing at the specific area. The integrated chip could successfully manipulate single cells to a specific position and lysis. The overall successful rate of cell tracking, positioning, and cell lysis is 80%. The average speed of cell driving was 17.74 μm/s. This technique will be developed for DNA extraction in biomolecular detection. It can simplify pre-treatment procedures for biotechnological analysis of samples.

  13. A novel mast cell co-culture microfluidic chip for the electrochemical evaluation of food allergen.

    Jiang, Hui; Jiang, Donglei; Zhu, Pei; Pi, Fuwei; Ji, Jian; Sun, Chao; Sun, Jiadi; Sun, Xiulan


    In this study a novel cell-to-cell electrochemical microfluidic chip was developed for qualitative and quantitative analysis of food allergen. Microfluidic cell culture, food allergen-induced cell morphological changes, and cell metabolism measurements were performed simultaneously using the aforementioned device. RBL-2H3 mast cells and ANA-1 macrophages have been used within a cell co-culture model to observe their allergic response when they are introduced to the antigen stimulus. Two cell cultivation microfluidic channels are located in the microfluidic chip, which is fabricated with four groups of gold electrodes, with an additional "capillary". In order to detect the allergic response, the cells were stimulated with dinitrophenylated bovine serum albumin (DNP-BSA) without anti-DNP IgE incubation. When exocytosis occurs, the cell-secreted inflammatory cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cell impedance changes were detected using cell-based electrochemical assay. Results indicate that the real-time cell allergic response are accurately monitored by this electrochemical microfluidic chip, which provides a general example of rapidly prototyped low-cost biosensor technology for applications in both food allergen detection and investigation. PMID:27108255

  14. Advancing interconnect density for spiking neural network hardware implementations using traffic-aware adaptive network-on-chip routers.

    Carrillo, Snaider; Harkin, Jim; McDaid, Liam; Pande, Sandeep; Cawley, Seamus; McGinley, Brian; Morgan, Fearghal


    The brain is highly efficient in how it processes information and tolerates faults. Arguably, the basic processing units are neurons and synapses that are interconnected in a complex pattern. Computer scientists and engineers aim to harness this efficiency and build artificial neural systems that can emulate the key information processing principles of the brain. However, existing approaches cannot provide the dense interconnect for the billions of neurons and synapses that are required. Recently a reconfigurable and biologically inspired paradigm based on network-on-chip (NoC) and spiking neural networks (SNNs) has been proposed as a new method of realising an efficient, robust computing platform. However, the use of the NoC as an interconnection fabric for large-scale SNNs demands a good trade-off between scalability, throughput, neuron/synapse ratio and power consumption. This paper presents a novel traffic-aware, adaptive NoC router, which forms part of a proposed embedded mixed-signal SNN architecture called EMBRACE (EMulating Biologically-inspiRed ArChitectures in hardwarE). The proposed adaptive NoC router provides the inter-neuron connectivity for EMBRACE, maintaining router communication and avoiding dropped router packets by adapting to router traffic congestion. Results are presented on throughput, power and area performance analysis of the adaptive router using a 90 nm CMOS technology which outperforms existing NoCs in this domain. The adaptive behaviour of the router is also verified on a Stratix II FPGA implementation of a 4 × 2 router array with real-time traffic congestion. The presented results demonstrate the feasibility of using the proposed adaptive NoC router within the EMBRACE architecture to realise large-scale SNNs on embedded hardware. PMID:22561008

  15. Designing a WISHBONE Protocol Network Adapter for an Asynchronous Network-on-Chip

    Soliman, Ahmed H M; El-Bably, M; Keshk, Hesham M A M


    The Scaling of microchip technologies, from micron to submicron and now to deep sub-micron (DSM) range, has enabled large scale systems-on-chip (SoC). In future deep submicron (DSM) designs, the interconnect effect will definitely dominate performance. Network-on-Chip (NoC) has become a promising solution to bus-based communication infrastructure limitations. NoC designs usually targets Application Specific Integrated Circuits (ASICs), however, the fabrication process costs a lot. Implementing a NoC on an FPGA does not only reduce the cost but also decreases programming and verification cycles. In this paper, an Asynchronous NoC has been implemented on a SPARTAN-3E\\textregistered device. The NoC supports basic transactions of both widely used on-chip interconnection standards, the Open Core Protocol (OCP) and the WISHBONE Protocol. Although, FPGA devices are synchronous in nature, it has been shown that they can be used to prototype a Global Asynchronous Local Synchronous (GALS) systems, comprising an Asynchr...

  16. Designing a WISHBONE Protocol Network Adapter for an Asynchronous Network-on-Chip

    Ahmed H M Soliman


    Full Text Available The Scaling of microchip technologies, from micron to submicron and now to deep sub-micron (DSM range, has enabled large scale systems-on-chip (SoC. In future deep submicron (DSM designs, the interconnect effect will definitely dominate performance. Network-on-Chip (NoC has become a promising solution to bus-based communication infrastructure limitations. NoC designs usually targets Application Specific Integrated Circuits (ASICs, however, the fabrication process costs a lot. Implementing a NoC on an FPGA does not only reduce the cost but also decreases programming and verification cycles. In this paper, an Asynchronous NoC has been implemented on a SPARTAN-3Eandamp;reg; device. The NoC supports basic transactions of both widely used on-chip interconnection standards, the Open Core Protocol (OCP and the WISHBONE Protocol. Although, FPGA devices are synchronous in nature, it has been shown that they can be used to prototype a Global Asynchronous Local Synchronous (GALS systems, comprising an Asynchronous NoC connecting IP cores operating in different clock domains.

  17. Full on-chip and area-efficient CMOS LDO with zero to maximum load stability using adaptive frequency compensation

    A full on-chip and area-efficient low-dropout linear regulator (LDO) is presented. By using the proposed adaptive frequency compensation (AFC) technique, full on-chip integration is achieved without compromising the LDO's stability in the full output current range. Meanwhile, the use of a compact pass transistor (the compact pass transistor serves as the gain fast roll-off output stage in the AFC technique) has enabled the LDO to be very area-efficient. The proposed LDO is implemented in standard 0.35 μm CMOS technology and occupies an active area as small as 220 x 320 μm2, which is a reduction to 58% compared to state-of-the-art designs using technologies with the same feature size. Measurement results show that the LDO can deliver 0-60 mA output current with 54 μA quiescent current consumption and the regulated output voltage is 1.8 V with an input voltage range from 2 to 3.3 V. (semiconductor integrated circuits)

  18. Raman-Spectroscopy Based Cell Identification on a Microhole Array Chip

    Ute Neugebauer


    Full Text Available Circulating tumor cells (CTCs from blood of cancer patients are valuable prognostic markers and enable monitoring responses to therapy. The extremely low number of CTCs makes their isolation and characterization a major technological challenge. For label-free cell identification a novel combination of Raman spectroscopy with a microhole array platform is described that is expected to support high-throughput and multiplex analyses. Raman spectra were registered from regularly arranged cells on the chip with low background noise from the silicon nitride chip membrane. A classification model was trained to distinguish leukocytes from myeloblasts (OCI-AML3 and breast cancer cells (MCF-7 and BT-20. The model was validated by Raman spectra of a mixed cell population. The high spectral quality, low destructivity and high classification accuracy suggests that this approach is promising for Raman activated cell sorting.

  19. Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications

    Qi Tang


    Full Text Available THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

  20. CHIP has a protective role against oxidative stress-induced cell death through specific regulation of Endonuclease G

    Lee, J.S.; Seo, T W; Yi, J. H.; K. S. Shin; Yoo, S. J.


    Oxidative stress is implicated in carcinogenesis, aging, and neurodegenerative diseases. The E3 ligase C terminus of Hsc-70 interacting protein (CHIP) has a protective role against various stresses by targeting damaged proteins for proteasomal degradation, and thus maintains protein quality control. However, the detailed mechanism by which CHIP protects cells from oxidative stress has not been demonstrated. Here, we show that depletion of CHIP led to elevated Endonuclease G (EndoG) levels and...

  1. Adaptive on-chip control of nano-optical fields with optoplasmonic vortex nanogates

    Boriskina, Svetlana V


    A major challenge for plasmonics as an enabling technology for quantum information processing is the realization of active spatio-temporal control of light on the nanoscale. The use of phase-shaped pulses or beams enforces specific requirements for on-chip integration and imposes strict design limitations. We introduce here an alternative approach, which is based on exploiting the strong sub-wavelength spatial phase modulation in the near-field of resonantly-excited high-Q optical microcavities integrated into plasmonic nanocircuits. Our theoretical analysis reveals the formation of areas of circulating powerflow (optical vortices) in the near-fields of optical microcavities, whose positions and mutual coupling can be controlled by tuning the microcavities parameters and the excitation wavelength. We show that optical powerflow though nanoscale plasmonic structures can be dynamically molded by engineering interactions of microcavity-induced optical vortices with noble-metal nanoparticles. The proposed strateg...

  2. An Adaptive Multiuser Chip-Rate Equalizer for CDMA Underwater Communication System

    HAN Jing; HUANG Jian-guo; SHEN Xiao-hong


    Direct-sequence code-division multiple access (CDMA) is considered for multiuser communication network in underwater acoustic channel, where extended multipath and rapid time-variability are encountered. To track and compensate the channel distortion, a decentralized hypothesis-feedback equalization (HFE) algorithm based on chip-rate update has been used[1]. But due to multiple access interference (MAI), its performance suffers degradation. For this reason, successive interference cancellation hypothesis-feedback equalization (SIC-HFE) algorithm is proposed, which combines the capabilities of HFE to track the time-varying channel and SIC implemented by cross-over feedback filters to cancel out the MAI effects between users. Simulation and experiment results show that the proposed algorithm can significantly improve the performance of asynchronous multiuser CDMA underwater communication system.

  3. On-chip constructive cell-network study (II: on-chip quasi-in vivo cardiac toxicity assay for ventricular tachycardia/fibrillation measurement using ring-shaped closed circuit microelectrode with lined-up cardiomyocyte cell network

    Yasuda Kenji


    Full Text Available Abstract Backgrounds Conventional in vitro approach using human ether-a-go-go related gene (hERG assay has been considered worldwide as the first screening assay for cardiac repolarization safety. However, it does not always oredict the potential QT prolongation risk or pro-arrhythmic risk correctly. For adaptable preclinical strategiesto evaluate global cardiac safety, an on-chip quasi-in vivo cardiac toxicity assay for lethal arrhythmia (ventricular tachyarrhythmia measurement using ring-shaped closed circuit microelectrode chip has been developed. Results The ventricular electrocardiogram (ECG-like field potential data, which includes both the repolarization and the conductance abnormality, was acquired from the self-convolutied extracellular field potentials (FPs of a lined-up cardiomyocyte network on a circle-shaped microelectrode in an agarose microchamber. When Astemisol applied to the closed-loop cardiomyocyte network, self-convoluted FP profile of normal beating changed into an early afterdepolarization (EAD like waveform, and then showed ventricular tachyarrhythmias and ventricular fibrilations (VT/Vf. QT-prolongation-like self-convoluted FP duration prolongation and its fluctuation increase was also observed according to the increase of Astemizole concentration. Conclusions The results indicate that the convoluted FPs of the quasi-in vivo cell network assay includes both of the repolarization data and the conductance abnormality of cardiomyocyte networks has the strong potential to prediction lethal arrhythmia.

  4. Cell Monitoring and Manipulation Systems (CMMSs based on Glass Cell-Culture Chips (GC3s

    Sebastian M. Buehler


    Full Text Available We developed different types of glass cell-culture chips (GC3s for culturing cells for microscopic observation in open media-containing troughs or in microfluidic structures. Platinum sensor and manipulation structures were used to monitor physiological parameters and to allocate and permeabilize cells. Electro-thermal micro pumps distributed chemical compounds in the microfluidic systems. The integrated temperature sensors showed a linear, Pt1000-like behavior. Cell adhesion and proliferation were monitored using interdigitated electrode structures (IDESs. The cell-doubling times of primary murine embryonic neuronal cells (PNCs were determined based on the IDES capacitance-peak shifts. The electrical activity of PNC networks was detected using multi-electrode arrays (MEAs. During seeding, the cells were dielectrophoretically allocated to individual MEAs to improve network structures. MEA pads with diameters of 15, 20, 25, and 35 µm were tested. After 3 weeks, the magnitudes of the determined action potentials were highest for pads of 25 µm in diameter and did not differ when the inter-pad distances were 100 or 170 µm. Using 25-µm diameter circular oxygen electrodes, the signal currents in the cell-culture media were found to range from approximately −0.08 nA (0% O2 to −2.35 nA (21% O2. It was observed that 60-nm thick silicon nitride-sensor layers were stable potentiometric pH sensors under cell-culture conditions for periods of days. Their sensitivity between pH 5 and 9 was as high as 45 mV per pH step. We concluded that sensorized GC3s are potential animal replacement systems for purposes such as toxicity pre-screening. For example, the effect of mefloquine, a medication used to treat malaria, on the electrical activity of neuronal cells was determined in this study using a GC3 system.

  5. DNA transfection of bone marrow mesenchymal stem cells using micro electroporation chips

    Deng, Peigang


    Experimental study of electroporation of bone marrow mesenchymal stem cells (MSCs) at the single-cell level was carried out on a micro EP chip by using single electric rectangular pulse. The threshold values of the electrode potential and pulse width for gas bubble generation on the micro electrodes due to electrolysis of water were revealed as 4.5 volt and 100 μs, respectively. Quantitative EP study was performed with various electric field strengths for various pulse widths, ranging from 20μs to 15ms. Over 1,000 single-cell EP results were used to construct an EP "phase diagram", which delineates the boundaries for (1) effective EP of MSCs and (2) electric cell lysis of MSCs. Finally, the micro EP chip showed successful transfection of the pEGFP-C1 plasmid into the MSCs by properly choosing the electric parameters from the EP "phase diagram". © 2011 IEEE.

  6. Chip-based optical microscopy for imaging membrane sieve plates of liver scavenger cells

    Helle, Øystein I.; Øie, Cristina I.; McCourt, Peter; Ahluwalia, Balpreet S.


    The evanescent field on top of optical waveguides is used to image membrane network and sieve-plates of liver endothelial cells. In waveguide excitation, the evanescent field is dominant only near the surface (~100-150 nm) providing a default optical sectioning by illuminating fluorophores in close proximity to the surface and thus benefiting higher signal-to-noise ratio. The sieve plates of liver sinusoidal endothelial cells are present on the cell membrane, thus near-field waveguide chip-based microscopy configuration is preferred over epi-fluorescence. The waveguide chip is compatible with optical fiber components allowing easy multiplexing to different wavelengths. In this paper, we will discuss the challenges and opportunities provided by integrated optical microscopy for imaging cell membranes.

  7. Self-adaptive phosphor coating technology for wafer-level scale chip packaging

    Zhou Linsong; Rao Haibo; Wang Wei; Wan Xianlong; Liao Junyuan; Wang Xuemei; Zhou Da


    A new self-adaptive phosphor coating technology has been successfully developed,which adopted a slurry method combined with a self-exposure process.A phosphor suspension in the water-soluble photoresist was applied and exposed to LED blue light itself and developed to form a conformal phosphor coating with selfadaptability to the angular distribution of intensity of blue light and better-performing spatial color uniformity.The self-adaptive phosphor coating technology had been successfully adopted in the wafer surface to realize a waferlevel scale phosphor conformal coating.The first-stage experiments show satisfying results and give an adequate demonstration of the flexibility of self-adaptive coating technology on application of WLSCP.

  8. A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

    Faigle, C.; Lautenschläger, F.; Whyte, G; Homewood, P.; Martín Badosa, Estela; Guck, J.


    The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetricall...

  9. Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses

    Bonk, Sebastian M.; Paul Oldorf; Rigo Peters; Werner Baumann; Jan Gimsa


    We developed a confined microfluidic cell culture system with a bottom plate made of a microscopic slide with planar platinum sensors for the measurement of acidification, oxygen consumption, and cell adhesion. The slides were commercial slides with indium tin oxide (ITO) plating or were prepared from platinum sputtering (100 nm) onto a 10-nm titanium adhesion layer. Direct processing of the sensor structures (approximately three minutes per chip) by an ultrashort pulse laser facilitated the ...

  10. Injection molded polymer chip for electrochemical and electrophysiological recordings from single cells

    Tanzi, Simone; Larsen, Simon Tylsgaard; Rafael J. Taboryski


    We present a novel method to fabricate an all in polymer injection molded chip for electrochemical cell recordings and lateral cell trapping. The complete device is molded in thermoplastic polymer and it results from assembling two halves. We tested spin-coated conductive polymer poly(3,4-ethylenedioxythiopene) and showed that it can be used as an electrode material for detecting neurotransmitters electrochemically in biosensors.

  11. On-chip manipulation of single microparticles, cells, and organisms using surface acoustic waves

    Ding, Xiaoyun; Lin, Sz-Chin Steven; Kiraly, Brian; Yue, Hongjun; Li, Sixing; Chiang, I-Kao; Shi, Jinjie; Benkovic, Stephen J.; Huang, Tony Jun


    Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve re...

  12. Novel sequential ChIP and simplified basic ChIP protocols for promoter co-occupancy and target gene identification in human embryonic stem cells

    Elayaperumal Anuratha


    Full Text Available Abstract Background The investigation of molecular mechanisms underlying transcriptional regulation, particularly in embryonic stem cells, has received increasing attention and involves the systematic identification of target genes and the analysis of promoter co-occupancy. High-throughput approaches based on chromatin immunoprecipitation (ChIP have been widely used for this purpose. However, these approaches remain time-consuming, expensive, labor-intensive, involve multiple steps, and require complex statistical analysis. Advances in this field will greatly benefit from the development and use of simple, fast, sensitive and straightforward ChIP assay and analysis methodologies. Results We initially developed a simplified, basic ChIP protocol that combines simplicity, speed and sensitivity. ChIP analysis by real-time PCR was compared to analysis by densitometry with the ImageJ software. This protocol allowed the rapid identification of known target genes for SOX2, NANOG, OCT3/4, SOX17, KLF4, RUNX2, OLIG2, SMAD2/3, BMI-1, and c-MYC in a human embryonic stem cell line. We then developed a novel Sequential ChIP protocol to investigate in vivo promoter co-occupancy, which is basically characterized by the absence of antibody-antigen disruption during the assay. It combines centrifugation of agarose beads and magnetic separation. Using this Sequential ChIP protocol we found that c-MYC associates with the SOX2/NANOG/OCT3/4 complex and identified a novel RUNX2/BMI-1/SMAD2/3 complex in BG01V cells. These two TF complexes associate with two distinct sets of target genes. The RUNX2/BMI-1/SMAD2/3 complex is associated predominantly with genes not expressed in undifferentiated BG01V cells, consistent with the reported role of those TFs as transcriptional repressors. Conclusion These simplified basic ChIP and novel Sequential ChIP protocols were successfully tested with a variety of antibodies with human embryonic stem cells, generated a number of novel

  13. On-chip clearing of arrays of 3-D cell cultures and micro-tissues.

    Grist, S M; Nasseri, S S; Poon, T; Roskelley, C; Cheung, K C


    Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 μm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear(T2); however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This on-chip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications. PMID:27493703

  14. A cell counting/sorting system incorporated with a microfabricated flow cytometer chip

    Yang, Sung-Yi; Hsiung, Suz-Kai; Hung, Yung-Ching; Chang, Chen-Min; Liao, Teh-Lu; Lee, Gwo-Bin


    Flow cytometry is a popular technique for counting and sorting individual cells. This study presents and demonstrates a new cell counting/sorting system integrated with several essential components including a micromachined flow cytometer chip device, an optical detection system and a data analysis and control system to achieve the functions of cell sample injection, optical signal detection and cell collection. By using MEMS technology, we have integrated several microfluidic components such as micro pneumatic pumps/valves onto a polymer-based chip device. Three pneumatic micropumps are used to provide the hydrodynamic driving force for both sample and sheath flows such that hydrodynamic flow focusing can be achieved, and a micro flow switch device comprising three pneumatic microvalves located downstream of the micro sample flow channel is used for cell collection. Cell samples of human lung cancer cells labelled with commercially available fluorescent dyes have been detected and collected successfully utilizing the developed device. The real-time image of dye-labelled cell samples being excited and detected can be monitored and observed through the LCD panel by a custom designed CCD/APD holder and moving stage. Finally, micro flow switch devices were used to successfully sort the cells into the desired outlet channel, and the counting results of the specific cell samples were monitored through the counting panel. The current study focuses on the setup of the overall system. The proposed flow cytometer system has several advantages such as portability, low cost and easy operation process. The size of the system is 37 cm × 16 cm × 18 cm and the weight is 3.5 kg. The error rate of counting and sorting was 1.5% and 2%, respectively. The sorting frequency of the microvalve device is calculated to be 120 cells min-1. The developed microfluidic chip device could be a promising tool for cell-based application fields such as profiling, counting and sorting.

  15. Innovative approaches to cell biomechanics from cell migration to on-chip manipulation

    Okeyo, Kennedy Omondi; Adachi, Taiji


    This book covers topics on mechanosensing, mechanotransduction, and actin cytoskeletal dynamics in cell motility. It will contribute to a better understanding of how cells functionally adapt to their mechanical environment as well as highlighting fundamental concepts for designing material niches for cell manipulation. With topics from multidisciplinary fields of the life sciences, medicine, and engineering, the book is the first of its kind, providing comprehensive, integrated coverage of innovative approaches to cell biomechanics. It provides a valuable resource for seniors and graduate students studying cell biomechanics, and is also suitable for researchers interested in the application of methods and strategies in connection with the innovative approaches discussed. Each section of the book has been supplemented with concrete examples and illustrations to facilitate understanding even for readers unfamiliar with cell biomechanics.

  16. BioMEMS for medicine: On-chip cell characterization and implantable microelectrodes

    Cheung, Karen C.; Renaud, Philippe


    This paper surveys a few of the emerging bioMEMS technologies at EPFL for improved, inexpensive health care. The lab-on-a-chip systems use dielectrophoretic forces to direct cell movement within microfluidic networks and impedance spectroscopy for label-free in-flow characterization of living cells. The implantable microelectrodes for neural applications are based on thin-film polymer foils with embedded microelectrodes for both recording and stimulation. Applications for these biomedical microdevices will include stem cell research, cancer cell characterization, drug discovery, treatments for neurological disorders, and neuroprosthetic devices.

  17. Programmable System on Chip Distributed Communication and Control Approach for Human Adaptive Mechanical System

    Ahmad A.M. Faudzi; Suzumori, K


    Problem statement: Communication and control are two main components in any Mechatronics system. They can be designed either by centralized or decentralized approach. Both approaches can be chosen based on application designed and specific requirements of the designer. In this study, decentralized or normally called distributed approach was selected to solved communication and control of a human adaptive mechanical system namely Intelligent Chair Tools (ICT). The ICT seating system is powered...

  18. Adaptation and dynamics of cat retinal ganglion cells.

    Enroth-Cugell, C; Shapley, R M


    1. The impulse/quantum (I/Q) ratio was measured as a function of background illumination for rod-dominated, pure central, linear square-wave responses of retinal ganglion cells in the cat.2. The I/Q ratio was constant at low backgrounds (dark adapted state) and inversely proportional to the 0.9 power of the background at high backgrounds (the light adapted state). There was an abrupt transition from the dark-adapted state to the light-adapted state.3. It was possible to define the adaptation level at a particular background as the ratio (I/Q ratio at that background)/(dark adapted I/Q ratio).4. The time course of the square-wave response was correlated with the adaptation level. The response was sustained in the dark-adapted state, partially transient at the transition level, and progressively more transient the lower the impulse/quantum ratio of the ganglion cell became. This was true both for on-centre and off-centre cells.5. The frequency response of the central response mechanism at different adaptation levels was measured. It was a low-pass characteristic in the dark-adapted state and became progressively more of a bandpass characteristic as the cell became more light-adapted.6. The rapidity of onset of adaptation was measured with a time-varying adapting light. The impulse/quantum ratio is reset within 100 msec of the onset of the conditioning light, and is kept at the new value throughout the time the conditioning light is on.7. These results can be explained by a nonlinear feedback model. In the model, it is postulated that the exponential function of the horizontal cell potential controls transmission from rods to bipolars. This model has an abrupt transition from dark- to light-adapted states, and its response dynamics are correlated with adaptation level. PMID:4747229

  19. On-Chip Single-Cell Lysis for Extracting Intracellular Material

    Ikeda, Norifumi; Tanaka, Nobuaki; Yanagida, Yasuko; Hatsuzawa, Takeshi


    A newly designed microfluidic chip with a pinched-channel structure and two pairs of electrodes has been developed to enable easier single-cell capture and lysis. The function of the chip was evaluated by introducing zucchini protoplast cells into the channel. In the first experiment, we attempted to break a cell using the through force of a triangular pinched structure via electroosmotic flow generated by outer electrodes. The pinched structure appeared to break the cell without applying the electric field to the cell directly; however, in this case, the breakable size of the cell was limited by the width of the pinched structure. The next attempt was to break cells regardless of their sizes using a pair of inner electrodes located under the pinched structure. The inner electrodes generated a gradient electric field around the captured cell by applying an alternative voltage to the electrodes. Captured cells with a diameter from 40 to 85 μm could be broken using the inner electrodes with a trapezoidal pinched structure, and the cells were successfully broken at 10 Vpp or less at a frequency of 1 MHz.

  20. Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies.

    Sun, Yung-Shin


    Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC) chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading) inlet and the parallel (in-line) inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies. PMID:27314318

  1. Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies

    Yung-Shin Sun


    Full Text Available Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading inlet and the parallel (in-line inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies.

  2. Regulation of the adaptive immune system by innate lymphoid cells

    Hepworth, Matthew R.; Sonnenberg, Gregory F.


    Innate lymphoid cells (ILCs) are a group of lymphocytes that promote rapid cytokine-dependent innate immunity, inflammation and tissue repair. In addition, a growing body of evidence suggests ILCs can influence adaptive immune cell responses. During fetal development a subset of ILCs orchestrate the generation and maturation of secondary lymphoid tissues. Following birth, ILCs continue to modulate adaptive immune cell responses indirectly through interactions with stromal cells in lymphoid ti...

  3. Wafer level fabrication of single cell dispenser chips with integrated electrodes for particle detection

    This work presents the microfabrication and experimental evaluation of a dispenser chip, designed for isolation and printing of single cells by combining impedance sensing and drop-on-demand dispensing. The dispenser chip features 50  ×  55 µm (width × height) microchannels, a droplet generator and microelectrodes for impedance measurements. The chip is fabricated by sandwiching a dry film photopolymer (TMMF) between a silicon and a Pyrex wafer. TMMF has been used to define microfluidic channels, to serve as low temperature (75 °C) bonding adhesive and as etch mask during 300 µm deep HF etching of the Pyrex wafer. Due to the novel fabrication technology involving the dry film resist, it became possible to fabricate facing electrodes at the top and bottom of the channel and to apply electrical impedance sensing for particle detection with improved performance. The presented microchip is capable of dispensing liquid and detecting microparticles via impedance measurement. Single polystyrene particles of 10 µm size could be detected with a mean signal amplitude of 0.39  ±  0.13 V (n=439) at particle velocities of up to 9.6 mm s−1 inside the chip. (paper)

  4. Efficient large volume electroporation of dendritic cells through micrometer scale manipulation of flow in a disposable polymer chip

    Selmeczi, Dávid; Hansen, Thomas Steen; Met, Özcan; Svane, Inge Marie; Larsen, Niels Bent


    We present a hybrid chip of polymer and stainless steel designed for high-throughput continuous electroporation of cells in suspension. The chip is constructed with two parallel stainless steel mesh electrodes oriented perpendicular to the liquid flow. The relatively high hydrodynamic resistance of...... performance of the chip is similar to that of the traditional electroporation cuvette, but without an upper limit on the number of cells to be electroporated. The device is constructed with two female Luer parts and can easily be integrated with other microfluidic components. Furthermore it is fabricated from...... injection molded polymer parts and commercially available stainless steel mesh, making it suitable for inexpensive mass production....


    吕桂泉; 许沈华; 牟瀚舟; 朱赤红; 羊正炎; 高永良; 楼洪坤; 刘祥麟; 杨文; 程勇


    To study the gene expression of high metastatic human ovarian carcinoma cell line (HO-8910PM) and to screen for novel metastasis- associated genes by cDNA microarray. Methods: The cDNA was retro-transcribed from equal quantity mRNA derived from tissues of highly metastatic ovarian carcinoma cell line and normal ovarian, and was labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BioDoor 4096 double dot human whole gene chip. The chip was scanned by scanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results: By applying the cDNA microarray we found: A total of 323 genes whose expression level were 3 times higher or lower in HO-8910PM cell than normal ovarian epithelium cell were screened out, with 71 higher and 252 lower respectively. Among these 10 were new genes. 67 genes showed expression difference bigger than 6 times between HO-8910PM cell and normal ovarian epithelium cell, among these genes 12 were higher, 55 lower, and two new genes were found. Conclusion: cDNA microarray technique is effective in screening the differentially expressed genes between human ovarian cancer cell line (HO-8910PM) and normal ovarian epithelium cell. Using the cDNA microarray to analyze of human ovarian cancer cell line gene expression profile difference will help the gene diagnosis, treatment and protection.

  6. The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM)

    Zheng, Guoan; Lee, Seung Ah; Antebi, Yaron; Elowitz, Michael B.; Yang, Changhuei


    We report a chip-scale lensless wide-field-of-view microscopy imaging technique, subpixel perspective sweeping microscopy, which can render microscopy images of growing or confluent cell cultures autonomously. We demonstrate that this technology can be used to build smart Petri dish platforms, termed ePetri, for cell culture experiments. This technique leverages the recent broad and cheap availability of high performance image sensor chips to provide a low-cost and automated microscopy soluti...

  7. Single cell membrane poration by bubble-induced microjets in a microfluidic chip.

    Li, Z G; Liu, A Q; Klaseboer, E; Zhang, J B; Ohl, C D


    This paper demonstrates membrane poration of a single suspension cell due to a fast liquid microjet. The jet is formed during the collapse of a laser induced bubble created at a variable stand-off distance from the target cell. The cell is trapped by a converging structure within a microfluidic chip. The asymmetrical growth and collapse of the cavitation bubble next to the cell lead to the microjetting, which deforms and porates the cell membrane. In the experiments, the membrane porations of myeloma cells are probed with the uptake of trypan blue. Time-resolved studies of the diffusion of trypan blue show a marked dependency on the bubble dynamics, i.e. the stand-off distance. The penetration length of the dye increases with shorter distances. Numerical simulations of the diffusion process agree with larger pores formed on the cell membrane. This method allows for a fast, repeatable, and localized rupture of membranes of individual cells in suspension. PMID:23364762

  8. Nucleic acid and protein extraction from electropermeabilized E. coli cells on a microfluidic chip

    Matos, T.; Senkbeil, Silja; Mendonça, A; Queiroz, J. A.; Kutter, Jörg Peter; Bulow, L.


    Due to the extensive use of nucleic acid and protein analysis of bacterial samples, there is a need for simple and rapid extraction protocols for both plasmid DNA and RNA molecules as well as reporter proteins like the green fluorescent protein (GFP). In this report, an electropermeability technique has been developed which is based on exposing E. coli cells to low voltages to allow extraction of nucleic acids and proteins. The flow-through electropermeability chip used consists of a microflu...

  9. Pyrolyzed Photoresist Electrodes for Integration in Microfluidic Chips for Transmitter Detection from Biological Cells

    Larsen, Simon Tylsgaard; Argyraki, Aikaterini; Amato, Letizia;


    In this study, we show how pyrolyzed photoresist carbon electrodes can be used for amperometric detection of potassium-induced transmitter release from large groups of neuronal PC 12 cells. This opens the way for the use of carbon film electrodes in microfabricated devices for neurochemical drug ...... by the difference in photoresist viscosity. By adding a soft bake step to the fabrication procedure, the flatness of pyrolyzed AZ 5214 electrodes could be improved which would facilitate their integration in microfluidic chip devices....

  10. 3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

    Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas


    Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering. PMID:27321481

  11. An integrated on-chip platform for negative enrichment of tumour cells.

    Bhuvanendran Nair Gourikutty, Sajay; Chang, Chia-Pin; Poenar, Daniel Puiu


    The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps. PMID:27344255

  12. An electrofusion chip with a cell delivery system driven by surface tension

    We have fabricated an electric cell fusion chip with an embedded cell delivery function driven by surface tension and evaluated its performance with several types of plant cells. The chip consists of a polydimethylsiloxane-based microchannel with a fusion chamber and gold–titanium (Au–Ti) electrodes. The velocity profiles of the microfluid in the channel and fusion chamber were calculated to predict cell movement, and the electric field distribution between the electrodes was also calculated in order to determine the appropriate electrode shape. The range of the fluid velocity in the fusion chamber is 20–50 µm s−1 and the measured speed of the cells is approximately 45 µm s−1, which is sufficiently slow for the motion of the cells in the fusion chamber to be monitored and controlled. We measured the variation of the pearl chain ratio with frequency for five kinds of plant cells, and determined that the optimal frequency for pearl chain formation is 1.5 MHz. The electrofusion of cells was successfully carried out under ac field (amplitude: 0.4–0.5 kV cm−1, frequency: 1.5 MHz) and dc pulse (amplitude: 1.0 kV cm−1, duration: 20 ms) conditions

  13. Single-Cell Electric Lysis on an Electroosmotic-Driven Microfluidic Chip with Arrays of Microwells

    Yu-Hung Chen


    Full Text Available Accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. An electroosmotic-driven microfluidic chip with arrays of 30-µm-diameter microwells was developed for single-cell electric lysis in the present study. The cellular occupancy in the microwells when the applied voltage was 5 V (82.4% was slightly higher than that at an applied voltage of 10 V (81.8%. When the applied voltage was increased to 15 V, the cellular occupancy in the microwells dropped to 64.3%. More than 50% of the occupied microwells contain individual cells. The results of electric lysis experiments at the single-cell level indicate that the cells were gradually lysed as the DC voltage of 30 V was applied; the cell was fully lysed after 25 s. Single-cell electric lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis.

  14. On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.

    Takanori Akagi

    Full Text Available Extracellular vesicles (EVs including exosomes and microvesicles have attracted considerable attention in the fields of cell biology and medicine. For a better understanding of EVs and further exploration of their applications, the development of analytical methods for biological nanovesicles has been required. In particular, considering the heterogeneity of EVs, methods capable of measuring individual vesicles are desired. Here, we report that on-chip immunoelectrophoresis can provide a useful method for the differential protein expression profiling of individual EVs. Electrophoresis experiments were performed on EVs collected from the culture supernatant of MDA-MB-231 human breast cancer cells using a measurement platform comprising a microcapillary electrophoresis chip and a laser dark-field microimaging system. The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG isotype control. Thus, on-chip immunoelectrophoresis could sensitively detect the over-expression of CD63 glycoproteins on EVs. Moreover, to explore the applicability of on-chip immunoelectrophoresis to cancer diagnosis, EVs collected from the blood of a mouse tumor model were analyzed by this method. By comparing the zeta potential distributions of EVs after their immunochemical reaction with normal IgG, and the anti-human CD63 and anti-human CD44 (cancer stem cell marker antibodies, EVs of tumor origin circulating in blood were differentially detected in the real sample. The result indicates that the present method is potentially applicable to liquid biopsy, a promising approach to the low-invasive diagnosis of cancer.

  15. Kicking off adaptive immunity: the discovery of dendritic cells

    Katsnelson, Alla


    In 1973, Ralph Steinman and Zanvil Cohn discovered an unusual looking population of cells with an unprecedented ability to activate naive T cells. Dubbed “dendritic cells,” these cells are now known as the primary instigators of adaptive immunity.

  16. Development of plasma-on-chip: Plasma treatment for individual cells cultured in media

    Kumagai, Shinya; Chang, Chun-Yao; Jeong, Jonghyeon; Kobayashi, Mime; Shimizu, Tetsuji; Sasaki, Minoru


    A device consisting of Si microwells and microplasma sources has been fabricated for plasma treatment of individual cells cultured in media. We named the device plasma-on-chip. The microwells have through-holes at the bottom where gas-liquid interfaces form when they are filled with media containing biological samples. The microplasma sources, which supply reactive species, are located on the back of each microwell. Through the gas-liquid interface, the reactive species are supplied to the cells. Chlorella cells were used to demonstrate the feasibility of the device and after three minutes of plasma treatment, the fluorescence intensity of Chlorella cells appeared to be decreased. Optical emission spectroscopy identified O and OH radicals in the plasma, which can affect the cells. In the analysis of biological samples such as human cells or tissues, this device raises the possibility of revealing the mechanisms of plasma medicine in more detail.

  17. Programmable System on Chip Distributed Communication and Control Approach for Human Adaptive Mechanical System

    Ahmad A.M. Faudzi


    Full Text Available Problem statement: Communication and control are two main components in any Mechatronics system. They can be designed either by centralized or decentralized approach. Both approaches can be chosen based on application designed and specific requirements of the designer. In this study, decentralized or normally called distributed approach was selected to solved communication and control of a human adaptive mechanical system namely Intelligent Chair Tools (ICT. The ICT seating system is powered by thirty six intelligent pneumatic actuators to facilitate investigation of chair shapes from spring and damping effect of seating and backrest surface. Three studies are proposed from the sitting experiments namely chair shapes, chair spring and chair damping properties. Approach: PSoC microcontroller was selected based on its features of having configurable analog and digital blocks. Its flexible modules and programmable peripherals ease designer in designing the communication and control of ICT in improved and faster way. Three protocols of USB, SPI and I2C were used for the communication system of ICT using PSoC. Flow charts of each communication protocols algorithms were discussed. On the other hand, the control system used PSoC’s ADC and counter modules to read inputs of pressure and encoder respectively. PWM module is used to control the valve and data communication was achieved using I2C module. Block diagram of unified control was discussed for further understandings of the control algorithms. Results: The PSoC specification, development design and experimental evaluation of ICT system are presented and discussed. Three studies of chair shapes, chair spring property and chair damping property from sitting experiment were shown. Conclusion/Recommendations: The PSoC microcontroller selection was discussed and application of its distributed communication and control was successfully applied to ICT. This distributed approach can be applied to other

  18. ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

    Faraco, Juliette; Lin, Ling; Kornum, Birgitte Rahbek;


    with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T...... cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells...

  19. Enhanced cell sorting and manipulation with combined optical tweezer and microfluidic chip technologies.

    Wang, Xiaolin; Chen, Shuxun; Kong, Marco; Wang, Zuankai; Costa, Kevin D; Li, Ronald A; Sun, Dong


    Sorting (or isolation) and manipulation of rare cells with high recovery rate and purity are of critical importance to a wide range of physiological applications. In the current paper, we report on a generic single cell manipulation tool that integrates optical tweezers and microfluidic chip technologies for handling small cell population sorting with high accuracy. The laminar flow nature of microfluidics enables the targeted cells to be focused on a desired area for cell isolation. To recognize the target cells, we develop an image processing methodology with a recognition capability of multiple features, e.g., cell size and fluorescence label. The target cells can be moved precisely by optical tweezers to the desired destination in a noninvasive manner. The unique advantages of this sorter are its high recovery rate and purity in small cell population sorting. The design is based on dynamic fluid and dynamic light pattern, in which single as well as multiple laser traps are employed for cell transportation, and a recognition capability of multiple cell features. Experiments of sorting yeast cells and human embryonic stem cells are performed to demonstrate the effectiveness of the proposed cell sorting approach. PMID:21918752

  20. Design, development and evaluation of a high spatial density CMOS chip for bidirectional communication with electrogenic cells

    Yegin, Ugur


    In this project, we present 2 CMOS chips designed in our institute with the aim of establishing a bio-electronic interface with electrically active cells. A measurement and control setup consisting of electronic components responsible for the control of the chips as well as the digitizazion and processing of the data they provide has also been developed. An intuitive LabView program faciliates the user interaction by allowing the setting of all analog bias voltages and digital controls, which...

  1. Simultaneous Measurement of Growth and Movement of Cells Exploiting On-Chip Single-Cell Cultivation Assay

    Umehara, Senkei; Hattori, Akihiro; Wakamoto, Yuichi; Yasuda, Kenji


    We have developed an on-chip single-cell microcultivation assay as a means of simultaneously observing the growth and movement of single bacterial cells during long-term cultivation. This assay enables the direct observation of single cells captured in microchambers fabricated on thin glass slides and having semipermeable membrane lids, in which the cells can swim within the space without escape for the long periods. Using this system, the relationship between the cell cycle and the tendency of movement was observed and it was found that the mean free path length did not change during the cell cycle, and that the growth and the swimming were not synchronized. The result indicates that the ability of movement of the cells was independent of the cell cycle.

  2. Towards autonomous lab-on-a-chip devices for cell phone biosensing.

    Comina, Germán; Suska, Anke; Filippini, Daniel


    Modern cell phones are a ubiquitous resource with a residual capacity to accommodate chemical sensing and biosensing capabilities. From the different approaches explored to capitalize on such resource, the use of autonomous disposable lab-on-a-chip (LOC) devices-conceived as only accessories to complement cell phones-underscores the possibility to entirely retain cell phones' ubiquity for distributed biosensing. The technology and principles exploited for autonomous LOC devices are here selected and reviewed focusing on their potential to serve cell phone readout configurations. Together with this requirement, the central aspects of cell phones' resources that determine their potential for analytical detection are examined. The conversion of these LOC concepts into universal architectures that are readable on unaccessorized phones is discussed within this context. PMID:26569446

  3. One Step Quick Detection of Cancer Cell Surface Marker by Integrated NiFe-based Magnetic Biosensing Cell Cultural Chip

    Chenchen Bao; Lei Chen; Tao Wang; Chong Lei; Furong Tian; Daxiang Cui; Yong Zhou


    RGD peptides has been used to detect cell surface integrin and direct clinical effective therapeutic drug selection. Herein we report that a quick one step detection of cell surface marker that was realized by a specially designed NiFe-based magnetic biosensing cell chip combined with functionalized magnetic nanoparti-cles. Magnetic nanoparticles with 20-30 nm in diameter were prepared by coprecipitation and modified with RGD-4C, and the resultant RGD-functionalized magnetic nanoparticles were used for targeting cancer cells cul-tured on the NiFe-based magnetic biosensing chip and distinguish the amount of cell surface receptor-integrin. Cell lines such as Calu3, Hela, A549, CaFbr, HEK293 and HUVEC exhibiting different integrin expression were chosen as test samples. Calu3, Hela, HEK293 and HUVEC cells were successfully identified. This approach has advantages in the qualitative screening test. Compared with traditional method, it is fast, sensitive, low cost, easy-operative, and needs very little human intervention. The novel method has great potential in applications such as fast clinical cell surface marker detection, and diagnosis of early cancer, and can be easily extended to other biomedical applications based on molecular recognition.

  4. Immunomagnetic Nano-Screening Chip for Circulating Tumor Cells Detection in Blood

    Horton, A. P.; Lane, N.; Tam, J.; Sokolov, K.; Garner, H. R.; Uhr, J. W.; Zhang, X. J.


    We present a novel method towards diagnose cancer at an early stage via a blood test. Early diagnosis is high on the future agenda of oncologists because of significant evidence that it will result in a higher cure rate. Capture of circulating tumor cells (CTCs) which are known to escape from carcinomas at an early stage offers such an opportunity. We design, fabricate and optimize the nanomagnetic-screening chip that captures the CTCs in microfluid, and further integrate the nano-chip with the new multispectral imaging system so that it can quantify different tumor markers and automate the entire instrument. Specifically, hybrid plasmonic (Fe2O3-core Au shell) nanoparticles, conjugated a collection of antibodies especially chosen to target breast cancer CTCs, with high magnetic susceptibility will be used for effective immunomagnetic CTC isolation. Greatly increased sensitivity over previous attempts is demonstrated by decreasing the length scale for interactions between the magnetic-nanoparticle-tagged CTCs and the isolative magnetic field, while increasing the effective cross-sectional area over which this interaction takes place. The screening chip is integrated with a novel hyperspectral microscopic imaging (HMI) platform capable of recording the entire emission spectra in a single pass evaluation. The combined system will precisely quantify up to 10 tumor markers on CTCs.

  5. Low-temperature bonded glass-membrane microfluidic device for in vitro organ-on-a-chip cell culture models

    Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin


    The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organson- a-chip", which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass based devices have long been utilised in the field of microfluidics but the integration of alternative functional elements within multi-layered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimised on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650 °C) and quartz/fused silica bonding (1050 °C) processes, this method maintains the integrity and functionality of the membrane (Tg 150 °C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 hours, indicating sufficient bond strength for long term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.

  6. Multilayer-based lab-on-a-chip systems for perfused cell-based assays

    Klotzbach, Udo; Sonntag, Frank; Grünzner, Stefan; Busek, Mathias; Schmieder, Florian; Franke, Volker


    A novel integrated technology chain of laser-microstructured multilayer foils for fast, flexible, and low-cost manufacturing of lab-on-a-chip devices especially for complex cell and tissue culture applications, which provides pulsatile fluid flow within physiological ranges at low media-to-cells ratio, was developed and established. Initially the microfluidic system is constructively divided into individual layers, which are formed by separate foils or plates. Based on the functional boundary conditions and the necessary properties of each layer, their corresponding foils and plates are chosen. In the third step, the foils and plates are laser microstructured and functionalized from both sides. In the fourth and last manufacturing step, the multiple plates and foils are joined using different bonding techniques like adhesive bonding, welding, etc. This multilayer technology together with pneumatically driven micropumps and valves permits the manufacturing of fluidic structures and perfusion systems, which spread out above multiple planes. Based on the established lab-on-a-chip platform for perfused cell-based assays, a multilayer microfluidic system with two parallel connected cell culture chambers was successfully implemented.

  7. Studies on adaptive responses in Chinese hamster cells

    For many years the possibility has been considered of low doses of radiation inducing adaptive responses in cells and organisms against the mutagenic effects of radiation. Currently, a number of experimental data appraise the existence of an adaptive response that is characterized by a decrease of radiation induced genetic damages. The understanding of the molecular mechanism involved in this phenomenon permits to estimate the effects and risks of low dose exposure. In this work, preliminary results of studies on the induction of adaptive response in cells subjected to different doses of ionizing radiation are presented

  8. Adaptation to optimal cell growth through self-organized criticality.

    Furusawa, Chikara; Kaneko, Kunihiko


    A simple cell model consisting of a catalytic reaction network is studied to show that cellular states are self-organized in a critical state for achieving optimal growth; we consider the catalytic network dynamics over a wide range of environmental conditions, through the spontaneous regulation of nutrient transport into the cell. Furthermore, we find that the adaptability of cellular growth to reach a critical state depends only on the extent of environmental changes, while all chemical species in the cell exhibit correlated partial adaptation. These results are in remarkable agreement with the recent experimental observations of the present cells. PMID:23003193

  9. Simplified variant of an optical chip to evaluate aggregation of red blood cells

    Toderi, Martín. A.; Riquelme, Bibiana D.; Castellini, Horacio V.


    Traditional techniques to evaluate the aggregation of red blood cells by optical methods require large sample volume and provide parameters that vary significantly from one method to another. A simplified variant of a chip system previously developed by Shin et al. (2009)1 based on light transmission for measuring erythrocyte aggregation is presented. Through a detailed analysis of intensity versus time curves, relevant information about erythrocyte aggregation and its variables is obtained. Parameters that provide more accuracy for the diagnosis of patients in order to have an immediate application in Clinical Medicine are proposed.

  10. Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses

    Sebastian M. Bonk


    Full Text Available We developed a confined microfluidic cell culture system with a bottom plate made of a microscopic slide with planar platinum sensors for the measurement of acidification, oxygen consumption, and cell adhesion. The slides were commercial slides with indium tin oxide (ITO plating or were prepared from platinum sputtering (100 nm onto a 10-nm titanium adhesion layer. Direct processing of the sensor structures (approximately three minutes per chip by an ultrashort pulse laser facilitated the production of the prototypes. pH-sensitive areas were produced by the sputtering of 60-nm Si3N4 through a simple mask made from a circuit board material. The system body and polydimethylsiloxane (PDMS molding forms for the microfluidic structures were manufactured by micromilling using a printed circuit board (PCB milling machine for circuit boards. The microfluidic structure was finally imprinted in PDMS. Our approach avoided the use of photolithographic techniques and enabled fast and cost-efficient prototyping of the systems. Alternatively, the direct production of metallic, ceramic or polymeric molding tools was tested. The use of ultrashort pulse lasers improved the precision of the structures and avoided any contact of the final structures with toxic chemicals and possible adverse effects for the cell culture in lab-on-a-chip systems.

  11. Flow fraction in charged rectangular microchannel to optimally design hydrodynamic filtration chip for cell sorting

    Chun, Myung-Suk; Jeong, Sohyun; Kim, Jae Hun; Lee, Tae Seok


    Among the passive separations, hydrodynamic filtration (HDF) can perform the fractionation of cells or particles by selective extraction of streamlines controlled by the flow fraction at each branch. Only the stream near the sidewall enters the branches as the focusing, with the amount of fluid leaving the main channel being determined by the flow distribution related to the hydraulic flow resistances. Its understanding is important, but in-depth consideration has not been treated until now. The virtual boundary of the fluid layer should be first specified, and the parabolic velocity profile starts to form from the steady state flow with high Péclet numbers. We computed the 3-dimensional flow profile at the rectangular cross-section with any aspect ratios, by considering electrokinetic transport coupled with the Poisson-Boltzmann and Navier-Stokes equations. The chip was designed with the parameters rigorously determined by the complete analysis of laminar flow for flow fraction and complicated networks of main and multi-branched channels for cell sorting into the finite number of subpopulations. For potential applications to the precise sorting, our designed microfluidic chip can be validated by applying model cells consisting of heterogeneous subpopulations. Supported by the KIST Institutional Program (No. 2E25382).

  12. Load Cell Response Correction Using Analog Adaptive Techniques

    Jafaripanah, Mehdi; Al-Hashimi, Bashir; White, Neil M.


    Load cell response correction can be used to speed up the process of measurement. This paper investigates the application of analog adaptive techniques in load cell response correction. The load cell is a sensor with an oscillatory output in which the measurand contributes to response parameters. Thus, a compensation filter needs to track variation in measurand whereas a simple, fixed filter is only valid at one load value. To facilitate this investigation, computer models for the load cell a...

  13. A multi-channel clogging-resistant lab-on-a-chip cell counter and analyzer

    Dai, Jie; Chiu, Yu-Jui; Lian, Ian; Wu, Tsung-Feng; Yang, Kecheng; Lo, Yu-Hwa


    Early signs of diseases can be revealed from cell detection in biofluids, such as detection of white blood cells (WBCs) in the peritoneal fluid for peritonitis. A lab-on-a-chip microfluidic device offers an attractive platform for such applications because of its small size, low cost, and ease of use provided the device can meet the performance requirements which many existing LoC devices fail to satisfy. We report an integrated microfluidic device capable of accurately counting low concentration of white blood cells in peritoneal fluid at 150 μl min-1 to offer an accurate (clogging, as well as excellent signal quality for unambiguous WBC count and WBC classification for certain diseases. These properties make the device a promising candidate for point-of-care applications.

  14. Using single cell cultivation system for on-chip monitoring of the interdivision timer in Chlamydomonas reinhardtii cell cycle

    Soloviev Mikhail


    Full Text Available Abstract Regulation of cell cycle progression in changing environments is vital for cell survival and maintenance, and different regulation mechanisms based on cell size and cell cycle time have been proposed. To determine the mechanism of cell cycle regulation in the unicellular green algae Chlamydomonas reinhardtii, we developed an on-chip single-cell cultivation system that allows for the strict control of the extracellular environment. We divided the Chlamydomonas cell cycle into interdivision and division phases on the basis of changes in cell size and found that, regardless of the amount of photosynthetically active radiation (PAR and the extent of illumination, the length of the interdivision phase was inversely proportional to the rate of increase of cell volume. Their product remains constant indicating the existence of an 'interdivision timer'. The length of the division phase, in contrast, remained nearly constant. Cells cultivated under light-dark-light conditions did not divide unless they had grown to twice their initial volume during the first light period. This indicates the existence of a 'commitment sizer'. The ratio of the cell volume at the beginning of the division phase to the initial cell volume determined the number of daughter cells, indicating the existence of a 'mitotic sizer'.

  15. DCB-adapted plant cells possess unique wall structure

    Shedletzky, E.; Shmuel, M. (Hebrew Univ., Jerusalem (Israel)); Delmer, D. (Hebrew Univ., Jerusalem (Israel) Michigan State Univ., East Lansing (USA)); Lamport, D. (Michigan State Univ., East Lansing (USA))


    Suspension-cultured cells of tomato (Lycopersicon esculentum VF 36) haven been adapted to growth on high concentrations of 2,6-dichloro-benzonitrile (DCB), an herbicide which inhibits cellulose biosynthesis. The mechanism of adaptation appears to rest largely on the ability of thee cells to divide and expand in the virtual absence of a cellulose-xyloglucan network. Walls of adapted cells growing on DCB also differ from non-adapted cells by having reduced levels of hydroxyproline in protein, both in bound and salt-elutable form, and in having a much higher proportion of homogalacturonon and rhamnogalacturonan-like polymers. Most of these latter polymers are apparently cross-linked in the wall via phenolic-esters and/or phenolic ether linkages, and these polymers appear to represent the major load-bearing network in thee unusual cell walls. The surprising finding that plant cells can survive in the virtual absence of a major load-bearing network in their primary cell walls indicates that plants possess remarkable flexibility for tolerating changes in wall composition.

  16. Ultrathin polyaniline film coated on an indium-tin oxide cell-based chip for study of anticancer effect

    Polyaniline emeraldine base (EB) coated indium-tin oxide (ITO) electrode was prepared for the construction of a cell-based chip. Ultrathin polyaniline PANI film on an ITO was electroactive at neutral pH without co-deposition of an acidic counterion. HeLa cells were cultured on a PANI/ITO substrate and utilized to assess the biological toxicity of anticancer drugs. Cell growth, cell viability and drug-related cell toxicity were evaluated by a cyclic voltammetry (CV) method under a neutral pH. We demonstrated the functionality of a PANI coated ITO electrode for use as a cell chip and found that PANI was a good surface for the HeLa cells to grow without any significant morphological changes.

  17. Characterization of bortezomib-adapted I-45 mesothelioma cells

    Peddaboina Chander


    Full Text Available Abstract Background Bortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy. Results The present study reports the development of I-45-BTZ-R, a bortezomib-resistant cell line, from the bortezomib-sensitive mesothelioma cell line I-45. I-45-BTZ-R cells showed no cross-resistance to the chemotherapeutic drugs cisplatin, 5-fluorouracil, and doxorubicin. Moreover, the bortezomib-adapted I-45-BTZ-R cells had decreased growth kinemics and did not over express proteasome subunit β5 (PSMB5 as compared to parental I-45 cells. I-45-BTZ-R cells and parental I-45 cells showed similar inhibition of proteasome activity, but I-45-BTZ-R cells exhibited much less accumulation of ubiquitinated proteins following exposure to 40 nm bortezomib. Further studies revealed that relatively low doses of bortezomib did not induce an unfolded protein response (UPR in the bortezomib-adapted cells, while higher doses induced UPR with concomitant cell death, as evidenced by higher expression of the mitochondrial chaperone protein Bip and the endoplasmic reticulum (ER stress-related pro-apoptotic protein CHOP. In addition, bortezomib exposure did not induce the accumulation of the pro-apoptotic proteins p53, Mcl-1S, and noxa in the bortezomib-adapted cells. Conclusion These results suggest that UPR evasion, together with reduced pro-apoptotic gene induction, accounts for bortezomib resistance in the bortezomib-adapted mesothelioma cell line I-45-BTZ-R.

  18. CMOS dielectrophoretic Lab-on-Chip platform for manipulation and monitoring of cells.

    Kyoungchul Park; Kabiri, Shideh; Sonkusale, Sameer


    We propose a novel Complementary Metal Oxide Semiconductor (CMOS) based Lab-on-Chip (LoC) platform for trapping, rotation and detection of cells and microorganism utilizing dielectrophoresis (DEP). DEP is a highly selective function of the permittivity, size and shape of the entity, and also depends on the permittivity of its environment; these dependencies can be used to identify and trap particles of interest with high precision. Real-time monitoring of such cellular manipulation is also desirable. Towards this goal, we have implemented a three-dimensional (3D) octa-pole electrode structure directly using the built-in metal layers of standard complementary metal-oxide-semiconductor (CMOS) process and demonstrate trapping and rotating of yeast cells. Moreover, we implement an impedance readout circuitry to monitor this process in situ. Paper presented both simulation and experimental results validating the platform. PMID:26738034

  19. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

    Juliette Faraco

    Full Text Available Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip. Three loci located outside the Human Leukocyte Antigen (HLA region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@, variants in two additional narcolepsy loci, Cathepsin H (CTSH and Tumor necrosis factor (ligand superfamily member 4 (TNFSF4, also called OX40L, attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

  20. Chip Multithreaded Consistency Model

    Zu-Song Li; Dan-Dan Huan; Wei-Wu Hu; Zhi-Min Tang


    Multithreaded technique is the developing trend of high performance processor. Memory consistency model is essential to the correctness, performance and complexity of multithreaded processor. The chip multithreaded consistency model adapting to multithreaded processor is proposed in this paper. The restriction imposed on memory event ordering by chip multithreaded consistency is presented and formalized. With the idea of critical cycle built by Wei-Wu Hu, we prove that the proposed chip multithreaded consistency model satisfies the criterion of correct execution of sequential consistency model. Chip multithreaded consistency model provides a way of achieving high performance compared with sequential consistency model and ensures the compatibility of software that the execution result in multithreaded processor is the same as the execution result in uniprocessor. The implementation strategy of chip multithreaded consistency model in Godson-2 SMT processor is also proposed. Godson-2 SMT processor supports chip multithreaded consistency model correctly by exception scheme based on the sequential memory access queue of each thread.

  1. An acoustically driven microliter flow chamber on a chip (muFCC) for cell-cell and cell-surface interaction studies.

    Schneider, Matthias F; Guttenberg, Zeno; Schneider, Stefan W; Sritharan, Kumudesh; Myles, Vanessa M; Pamukci, Umut; Wixforth, Achim


    A novel method for pumping very small volumes of liquid by using surface acoustic waves is employed to create a microfluidic flow chamber on a chip. It holds a volume of only a few mul and its planar design provides complete architectural freedom. This allows for the reconstruction of even complex flow scenarios (e.g. curvatures, bifurcations and stenosis). Addition of polymer walls to the planar fluidic track enables cell culturing on the chip surface and the investigation of cell-cell adhesion dynamics under flow. We demonstrate the flexibility of the system for application in many areas of microfluidic investigations including blood clotting phenomena under various flow conditions and the investigation of different stages of cell adhesion. PMID:18306189

  2. On-chip cell lysis by antibacterial non-leaching reusable quaternary ammonium monolithic column.

    Aly Saad Aly, Mohamed; Gauthier, Mario; Yeow, John


    Reusable antibacterial non-leaching monolithic columns polymerized in microfluidic channels designed for on-chip cell lysis applications were obtained by the photoinitiated free radical copolymerization of diallyldimethylammonium chloride (DADMAC) and ethylene glycol diacrylate (EGDA) in the presence of a porogenic solvent. The microfluidic channels were fabricated in cross-linked poly(methyl methacrylate) (X-PMMA) substrates by laser micromachining. The monolithic columns have the ability to inhibit the growth of, kill and efficiently lyse Gram-positive Micrococcus luteus (Schroeter) (ATCC 4698) and Kocuria rosea (ATCC 186), and Gram-negative bacteria Pseudomonas putida (ATCC 12633) and Escherichia coli (ATCC 35218) by mechanically shearing the bacterial membrane when forcing the cells to pass through the narrow pores of the monolithic column, and simultaneously disintegrating the cell membrane by physical contact with the antibacterial surface of the column. Cell lysis was confirmed by off-chip PCR without the need for further purification. The influence of the cross-linking monomer on bacterial growth inhibition, leaching, lysis efficiency of the monolithic column and its mechanical stability within the microfluidic channel were investigated and analyzed for three different cross-linking monomers: ethylene glycol dimethacrylate (EGDA), ethylene glycol dimethacrylate (EGDMA) and 1,6-hexanediol dimethacrylate (1,6-HDDMA). Furthermore, the bonding efficiency of two X-PMMA substrates with different cross-linking levels was studied. The monolithic columns were shown to be stable, non-leaching, and reusable for over 30 lysis cycles without significant performance degradation or DNA carryover when they were back-flushed between lysis cycles. PMID:26671610

  3. On-chip lithium cells for electrical and structural characterization of single nanowire electrodes

    We present a transmission electron microscopy (TEM)-compatible, hybrid nanomachined, on-chip construct for probing the structural and electrical changes in individual nanowire electrodes during lithium insertion. We have assembled arrays of individual β-phase manganese dioxide (β-MnO2) nanowires (NWs), which are employed as a model material system, into functional electrochemical cells through a combination of bottom-up (dielectrophoresis) and top-down (silicon nanomachining) unit processes. The on-chip NWs are electrochemically lithiated inside a helium-filled glovebox and their electrical conductivity is studied as a function of incremental lithium loading during initial lithiation. We observe a dramatic reduction in NW conductivity (on the order of two to three orders in magnitude), which is not reversed when the lithium is extracted from the nanoelectrode. This conductivity change is attributed to an increase in lattice disorder within the material, which is observed from TEM images of the lithiated NWs. Furthermore, electron energy loss spectroscopy (EELS) was employed to confirm the reduction in valence state of manganese, which occurs due to the transformation of MnO2 to LixMnO2. (papers)

  4. Contrast Adaptation Decreases Complexity in Retinal Ganglion Cell Spike Train

    WANG Guang-Li; HUANG Shi-Yong; ZHANG Ying-Ying; LIANG Pei-Ji


    @@ The difference in temporal structures of retinal ganglion cell spike trains between spontaneous activity and firing activity after contrast adaptation is investigated. The Lempel-Ziv complexity analysis reveals that the complexity of the neural spike train decreases after contrast adaptation. This implies that the behaviour of the neuron becomes ordered, which may carry relevant information about the external stimulus. Thus, during the neuron activity after contrast adaptation, external information could be encoded in forms of some certain patterns in the temporal structure of spike train that is significantly different, compared to that of the spike train during spontaneous activity, although the firing rates in spontaneous activity and firing activity after contrast adaptation are sometime similar.

  5. Monolithically integrated biophotonic lab-on-a-chip for cell culture and simultaneous pH monitoring

    Munoz-Berbel, Xavier; Rodriguez-Rodriguez, Rosalia; Vigues, Nuria; Demming, Stefanie; Mas, Jordi; Buettgenbach, Stephanus; Verpoorte, Elisabeth; Ortiz, Pedro; Llobera, Andreu


    A poly(dimethylsiloxane) biophotonic lab-on-a-chip (bioPhLoC) containing two chambers, an incubation chamber and a monitoring chamber for cell retention/proliferation and pH monitoring, respectively, is presented. The bioPhLoC monolithically integrates a filter with 3 mu m high size-exclusion microc

  6. A three-dimensional cell-laden microfluidic chip for in vitro drug metabolism detection

    Three-dimensional tissue platforms are rapidly becoming the method of choice for quantification of the heterogeneity of cell populations for many diagnostic and drug therapy applications. Microfluidic sensors and the integration of sensors with microfluidic systems are often described as miniature versions of their macro-scale counterparts. This technology presents unique advantages for handling costly and difficult-to-obtain samples and reagents as a typical system requires between 100 nL to 10 µL of working fluid. The fabrication of a fully functional cell-based biosensor utilizes both biological patterning and microfabrication techniques. A digital micro-mirror (photolithographic) system is initiated to construct the tissue platform while a cell printer is used to precisely embed the cells within the construct. Tissue construct developed with these technologies will provide an early diagnostic of a drug's potential use. A three-dimensional interconnected microfluidic environment has the potential to eliminate the limitations of the traditional mainstays of two-dimensional investigations. This paper illustrates an economical and an innovative approach of fabricating a three-dimensional cell-laden microfluidic chip for detecting drug metabolism. (paper)

  7. Cell cycle control after DNA damage: arrest, recovery and adaptation

    DNA damage triggers surveillance mechanisms, the DNA checkpoints, that control the genome integrity. The DNA checkpoints induce several responses, either cellular or transcriptional, that favor DNA repair. In particular, activation of the DNA checkpoints inhibits cell cycle progression in all phases, depending on the stage when lesions occur. These arrests are generally transient and cells ultimately reenter the cell division cycle whether lesions have been repaired (this process is termed 'recovery') or have proved un-repairable (this option is called 'adaptation'). The mechanisms controlling cell cycle arrests, recovery and adaptation are largely conserved among eukaryotes, and much information is now available for the yeast Saccharomyces cerevisiae, that is used as a model organism in these studies. (author)

  8. Screening radiosensitizing-related genes mediated by elemene in lung adenocarcinoma A549 cells by using gene chip

    Objective: To screen radiosensitizing-related genes mediated by elemene in lung adenocarcinoma A549 cells by using gene chip. Methods: MTT test was used to calculate the IC50 of elemene. (1) The effect of radiosensitivity was detected by colony forming assay. A549 cells were divided into 2 groups: radiation group and radiation + elemene group. Oligonucleotide chip was used to screen the gene expression changes of A549 cells from these 2 groups. The up-regulated gene Egr-1 and the down-regulated gene CyclinD1 were selected to undergo RT-PCR so as to confirm the reliability of the result. Results: MTT test showed the elemene inhibited the proliferation of the A549 cells dose-dependently. The IC50 value of elemene on the A549 cells was 120 mg/L. (2) 10 mg/L elemene had radiosensitising effect on A549 cells.The values of SERD0 and SERDq obtained from the survival curve were (1.54±0. 20) and (1.43±0.15) respectively. Gene chip screened 122 differentially-expressed genes, including 89 up-regulated genes and 33 down-regulated genes. (3) These altered genes could be related to cell structure, substance metabolism,cell proliferation, cell differentiation, signal transduction, material transport, DNA repair, apoptosis, immune response and so forth. The RT-PCR results of Egr-1 and Cyclin D1 were consistent with the gene chip analysis. Conclusions: The mechanism of elemene enhancing the radiosensitivity of lung adenocarcinoma A549 cells is the result of participation and collaboration of multiple genes. Further study of the newly-discovered differentially-expressed gene helps find out new radiosensitizational targets of elemene. (authors)

  9. Isolation of cells for selective treatment and analysis using a magnetic microfluidic chip

    Yassine, O.


    This study describes the development and testing of a magnetic microfluidic chip (MMC) for trapping and isolating cells tagged with superparamagnetic beads (SPBs) in a microfluidic environment for selective treatment and analysis. The trapping and isolation are done in two separate steps; first, the trapping of the tagged cells in a main channel is achieved by soft ferromagnetic disks and second, the transportation of the cells into side chambers for isolation is executed by tapered conductive paths made of Gold (Au). Numerical simulations were performed to analyze the magnetic flux and force distributions of the disks and conducting paths, for trapping and transporting SPBs. The MMC was fabricated using standard microfabrication processes. Experiments were performed with E. coli (K12 strand) tagged with 2.8 μm SPBs. The results showed that E. coli can be separated from a sample solution by trapping them at the disk sites, and then isolated into chambers by transporting them along the tapered conducting paths. Once the E. coli was trapped inside the side chambers, two selective treatments were performed. In one chamber, a solution with minimal nutrition content was added and, in another chamber, a solution with essential nutrition was added. The results showed that the growth of bacteria cultured in the second chamber containing nutrient was significantly higher, demonstrating that the E. coli was not affected by the magnetically driven transportation and the feasibility of performing different treatments on selectively isolated cells on a single microfluidic platform.

  10. Nanoelectromechanical Chip (NELMEC) Combination of Nanoelectronics and Microfluidics to Diagnose Epithelial and Mesenchymal Circulating Tumor Cells from Leukocytes.

    Hosseini, Seied Ali; Abdolahad, Mohammad; Zanganeh, Somayeh; Dahmardeh, Mahyar; Gharooni, Milad; Abiri, Hamed; Alikhani, Alireza; Mohajerzadeh, Shams; Mashinchian, Omid


    An integrated nano-electromechanical chip (NELMEC) has been developed for the label-free distinguishing of both epithelial and mesenchymal circulating tumor cells (ECTCs and MCTCs, respectively) from white blood cells (WBCs). This nanoelectronic microfluidic chip fabricated by silicon micromachining can trap large single cells (>12 µm) at the opening of the analysis microchannel arrays. The nature of the captured cells is detected using silicon nanograss (SiNG) electrodes patterned at the entrance of the channels. There is an observable difference between the membrane capacitance of the ECTCs and MCTCs and that of WBCs (measured using SiNG electrodes), which is the key indication for our diagnosis. The NELMEC chip not only solves the problem of the size overlap between CTCs and WBCs but also detects MCTCs without the need for any markers or tagging processes, which has been an important problem in previously reported CTC detection systems. The great conductivity of the gold-coated SiNG nanocontacts as well as their safe penetration into the membrane of captured cells, facilitate a precise and direct signal extraction to distinguish the type of captured cell. The results achieved from epithelial (MCF-7) and mesenchymal (MDA-MB231) breast cancer cells circulated in unprocessed blood suggest the significant applications for these diagnostic abilities of NELMEC. PMID:26727927

  11. A Single Cell Extraction Chip Using Vibration-Induced Whirling Flow and a Thermo-Responsive Gel Pattern

    Takeshi Hayakawa


    Full Text Available We propose a single cell extraction chip with an open structure, which utilizes vibration-induced whirling flow and a single cell catcher. By applying a circular vibration to a micropillar array spiral pattern, a whirling flow is induced around the micropillars, and target cells are transported towards the single cell catcher placed at the center of the spiral. The single cell catcher is composed of a single-cell-sized hole pattern of thermo-responsive gel. The gel swells at low temperatures (≲32 ◦C and shrinks at high temperatures (≳32 ◦C, therefore, its volume expansion can be controlled by an integrated microheater. When the microheater is turned on, a single cell is trapped by the hole pattern of the single cell catcher. Then, when the microheater is turned off, the single cell catcher is cooled by the ambient temperature. The gel swells at this temperature, and the hole closes to catch the single cell. The caught cell can then be released into culture wells on a microtiter plate by heating the gel again. We conducted single cell extraction with the proposed chip and achieved a 60% success rate, of which 61% cells yielded live cells.

  12. The individual-cell-based cryo-chip for the cryopreservation, manipulation and observation of spatially identifiable cells. I: Methodology

    Thaele Michael


    Full Text Available Abstract Background Cryopreservation is the only widely applicable method of storing vital cells for nearly unlimited periods of time. Successful cryopreservation is essential for reproductive medicine, stem cell research, cord blood storage and related biomedical areas. The methods currently used to retrieve a specific cell or a group of individual cells with specific biological properties after cryopreservation are quite complicated and inefficient. Results The present study suggests a new approach in cryopreservation, utilizing the Individual Cell-based Cryo-Chip (i3C. The i3C is made of materials having appropriate durability for cryopreservation conditions. The core of this approach is an array of picowells, each picowell designed to maintain an individual cell during the severe conditions of the freezing - thawing cycle and accompanying treatments. More than 97% of cells were found to retain their position in the picowells throughout the entire freezing - thawing cycle and medium exchange. Thus the comparison between pre-freezing and post-thawing data can be achieved at an individual cell resolution. The intactness of cells undergoing slow freezing and thawing, while residing in the i3C, was found to be similar to that obtained with micro-vials. However, in a fast freezing protocol, the i3C was found to be far superior. Conclusions The results of the present study offer new opportunities for cryopreservation. Using the present methodology, the cryopreservation of individual identifiable cells, and their observation and retrieval, at an individual cell resolution become possible for the first time. This approach facilitates the correlation between cell characteristics before and after the freezing - thawing cycle. Thus, it is expected to significantly enhance current cryopreservation procedures for successful regenerative and reproductive medicine.

  13. Monocyte-derived dendritic cells in innate and adaptive immunity.

    León, Beatriz; Ardavín, Carlos


    Monocytes have been classically considered essential elements in relation with innate immune responses against pathogens, and inflammatory processes caused by external aggressions, infection and autoimmune disease. However, although their potential to differentiate into dendritic cells (DCs) was discovered 14 years ago, their functional relevance with regard to adaptive immune responses has only been uncovered very recently. Studies performed over the last years have revealed that monocyte-derived DCs play an important role in innate and adaptive immunity, due to their microbicidal potential, capacity to stimulate CD4(+) and CD8(+) T-cell responses and ability to regulate Immunoglobulin production by B cells. In addition, monocyte-derived DCs not only constitute a subset of DCs formed at inflammatory foci, as previously thought, but also comprise different subsets of DCs located in antigen capture areas, such as the skin and the intestinal, respiratory and reproductive tracts. PMID:18362945

  14. Fully solution-processed organic light-emitting electrochemical cells (OLEC) with inkjet-printed micro-lenses for disposable lab-on-chip applications at ambient conditions

    Shu, Zhe; Pabst, Oliver; Beckert, Erik; Eberhardt, Ramona; Tünnermann, Andreas


    Microfluidic lab-on-chip devices can be used for chemical and biological analyses such as DNA tests or environmental monitoring. Such devices integrate most of the basic functionalities needed for scientific analysis on a microfluidic chip. When using such devices, cost and space-intensive lab equipment is no longer necessary. However, in order to make a monolithic and cost-efficient/disposable microfluidic sensing device, direct integration of the excitation light source for fluorescent sensing is often required. To achieve this, we introduce a fully solution processable deviation of OLEDs, organic light-emitting electrochemical cells (OLECs), as a low-cost excitation light source for a disposable microfluidic sensing platform. By mixing metal ions and a solid electrolyte with light-emitting polymers as active materials, an in-situ doping and in-situ PN-junction can be generated within a three layer sandwich device. Thanks to this doping effect, work function adaptation is not necessary and air-stable electrode can be used. An ambient manufacturing process for fully solution-processed OLECs is presented, which consist of a spin-coated blue light-emitting polymer plus dopants on an ITO cathode and an inkjet-printed PEDOT:PSS transparent top anode. A fully transparent blue OLEC is able to obtain light intensity > 2500 cd/m2 under pulsed driving mode and maintain stable after 1000 cycles, which fulfils requirements for simple fluorescent on-chip sensing applications. However, because of the large refractive index difference between substrates and air, about 80% of emitted light is trapped inside the device. Therefore, inkjet printed micro-lenses on the rear side are introduced here to further increase light-emitting brightness.

  15. A Clark-type oxygen chip for in situ estimation of the respiratory activity of adhering cells.

    Wu, Ching-Chou; Luk, Hsiang-Ning; Lin, Yen-Ting Tsai; Yuan, Chia-Yin


    A Clark-type oxygen chip consisting of a polydimethylsiloxane (PDMS) reservoir containing an amino group-modified PDMS oxygen-permeable membrane (OPM) and a glass substrate containing a three-electrode detector has been constructed by using microfabrication techniques, and it is utilized for in situ measurement of the respiration activity of adhering cells. Use of the alginate sol electrolyte and the electroplating Ag/AgCl pseudo-reference electrode can effectively diminish the crosstalk between the electrochemical electrodes and supply a stable potential for the detection of dissolved oxygen, respectively. The Clark-type oxygen chips possess only 1.00% residual current, response time of 13.4s and good linearity with a correlation coefficient of 0.9933. The modification of amino groups for the OPM obviously facilitates the adhesion of HeLa cells onto the PDMS OPM surface and allows the cells to spread after 2h of incubation. The oxygen consumption of the cells in the cell-adhesion process increases with the adhesion time, and the increment of cellular oxygen consumption per minute reaches a maximum after 30 min of incubation. Moreover, the change in the respiration activity of adhering HeLa cells stimulated by the high concentration of glucose or propofol anaesthetic can be monitored in real time with the Clark-type oxygen chip. PMID:20188913

  16. Highly efficient and selective isolation of rare tumor cells using a microfluidic chip with wavy-herringbone micro-patterned surfaces.

    Wang, Shunqiang; Thomas, Antony; Lee, Elaine; Yang, Shu; Cheng, Xuanhong; Liu, Yaling


    Circulating tumor cells (CTCs) in peripheral blood have been recognized as a general biomarker for diagnosing cancer and providing guidance for personalized treatments. Yet due to their rarity, the challenge for their clinical utility lies in the efficient isolation while avoiding the capture of other non-targeted white blood cells (WBCs). In this paper, a wavy-herringbone (HB) microfluidic chip coated with antibody directly against epithelial cell adhesion molecule (anti-EpCAM) was developed for highly efficient and selective isolation of tumor cells from tumor cell-spiked whole blood samples. By extending the concept of the hallmark HB-Chip in the literature, the wavy-HB chip not only achieves high capture efficiency (up to 85.0%) by micro-vortexes induced by HB structures, but also achieves high purity (up to 39.4%) due to the smooth wavy microstructures. These smooth wavy-HB structures eliminate the ultra-low shear rate regions in the traditional grooved-HB structures that lead to non-specific trapping of cells. Compared with the grooved-HB chip with sharp corners, the wavy-HB chip shows significantly higher purity while maintaining similarly high capture efficiency. Furthermore, the wavy-HB chip has up to 11% higher captured cell viability over the grooved-HB chip. The distributions of tumor cells and WBCs along the grooves and waves are investigated to help understand the mechanisms behind the better performance of the wavy-HB chip. The wavy-HB chip may serve as a promising platform for CTC capture and cancer diagnosis. PMID:26907962

  17. Relation between radio-adaptive response and cell to cell communication

    Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  18. Imaging live cells at high spatiotemporal resolution for lab-on-a-chip applications.

    Chin, Lip Ket; Lee, Chau-Hwang; Chen, Bi-Chang


    Conventional optical imaging techniques are limited by the diffraction limit and difficult-to-image biomolecular and sub-cellular processes in living specimens. Novel optical imaging techniques are constantly evolving with the desire to innovate an imaging tool that is capable of seeing sub-cellular processes in a biological system, especially in three dimensions (3D) over time, i.e. 4D imaging. For fluorescence imaging on live cells, the trade-offs among imaging depth, spatial resolution, temporal resolution and photo-damage are constrained based on the limited photons of the emitters. The fundamental solution to solve this dilemma is to enlarge the photon bank such as the development of photostable and bright fluorophores, leading to the innovation in optical imaging techniques such as super-resolution microscopy and light sheet microscopy. With the synergy of microfluidic technology that is capable of manipulating biological cells and controlling their microenvironments to mimic in vivo physiological environments, studies of sub-cellular processes in various biological systems can be simplified and investigated systematically. In this review, we provide an overview of current state-of-the-art super-resolution and 3D live cell imaging techniques and their lab-on-a-chip applications, and finally discuss future research trends in new and breakthrough research areas of live specimen 4D imaging in controlled 3D microenvironments. PMID:27121367

  19. A multi-channel clogging-resistant lab-on-a-chip cell counter and analyzer

    Early signs of diseases can be revealed from cell detection in biofluids, such as detection of white blood cells (WBCs) in the peritoneal fluid for peritonitis. A lab-on-a-chip microfluidic device offers an attractive platform for such applications because of its small size, low cost, and ease of use provided the device can meet the performance requirements which many existing LoC devices fail to satisfy. We report an integrated microfluidic device capable of accurately counting low concentration of white blood cells in peritoneal fluid at 150 μl min−1 to offer an accurate (<3% error) and fast (∼10 min/run) WBC count. Utilizing the self-regulating hydrodynamic properties and a unique architecture in the design, the device can achieve higher flow rate (500–1000 μl min−1), continuous running for over 5 h without clogging, as well as excellent signal quality for unambiguous WBC count and WBC classification for certain diseases. These properties make the device a promising candidate for point-of-care applications. (paper)

  20. On-chip manipulation of single microparticles, cells, and organisms using surface acoustic waves

    Ding, Xiaoyun; Lin, Sz-Chin Steven; Kiraly, Brian; Yue, Hongjun; Li, Sixing; Chiang, I-Kao; Shi, Jinjie; Benkovic, Stephen J.; Huang, Tony Jun


    Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e., Caenorhabditis elegans) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers’ compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering. PMID:22733731

  1. An asynchronous finite-state-machine-based buck-boost converter for on-chip adaptive power supply

    Fernández, Daniel; Madrenas Boadas, Jordi; Alarcón Cot, Eduardo José


    In this paper we present an asynchronous finite-state machine digital controller co-integrated with an on-chip non-inverting buck-boost power converter with dynamic signal-tracking capabilities. The mostly-digital controller functionally implements a non-PWM zone-wise control law through asynchronous circuitry, thus exhibiting self-timed minimum latency and ultra low power operation due to gate switching activity. Experimental results on a 0.35 lm CMOS technology demonstrate an efficien...

  2. 5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

    Hedi Harizi


    Full Text Available 5-lipoxygenase (5-LO pathway is the major source of potent proinflammatory leukotrienes (LTs issued from the metabolism of arachidonic acid (AA, and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatory and proinflammatory effects are mediated through extracellular specific G-protein-coupled receptors. Despite their role in inflammatory cells, such as neutrophils and macrophages, LTs may have important effects on dendritic cells (DC-mediated adaptive immunity. Several lines of evidence show that DC not only are important source of LTs, but also become targets of their actions by producing other lipid mediators and proinflammatory molecules. This review focuses on advances in 5-LO pathway biology, the production of LTs from DC and their role on various cells of immune system and in adaptive immunity.

  3. Single-Cell-Arrayed Agarose Chip for in Situ Analysis of Cytotoxicity and Genotoxicity of DNA Cross-Linking Agents.

    Li, Lili; Wang, Weixing; Ding, Mingyu; Luo, Guoan; Liang, Qionglin


    Development of approach or device to allow continuous multiple measurements, such as integrating cytotoxic and genotoxic analysis, is quite appealing for study of the drug's activity and mechanism of action or resistance. In this study, a single-cell-arrayed agarose chip system was developed to combine cell cultivation with subsequent in situ analysis of cytotoxicity and genotoxicity of the chemotherapeutic agent. The modified alkaline comet assay coupled with the Live/Dead assay was used to monitor the interstrand cross-links (ICLs) formation and the cytotoxic effects in different glioma cell lines. In addition, the ICL-induced double strand breaks (DSBs) was measured on the chip to reflect the level of ICLs indirectly. Compared with the traditional methods, the microarray agarose device offers higher throughput, reproducibility, and robustness, exhibiting good potential for high-content drug screening. PMID:27269449

  4. Adaptive switching frequency buck DC—DC converter with high-accuracy on-chip current sensor

    A current-mode PWM buck DC—DC converter is proposed. With the high-accuracy on-chip current sensor, the switching frequency can be selected automatically according to load requirements. This method improves efficiency and obtains an excellent transient response. The high accuracy of the current sensor is achieved by a simple switch technique without an amplifier. This has the direct benefit of reducing power dissipation and die size. Additionally, a novel soft-start circuit is presented to avoid the inrush current at the starting up state. Finally, this DC—DC converter is fabricated with the 0.5 μm standard CMOS process. The chip occupies 3.38 mm2. The accuracy of the proposed current sensor can achieve 99.5% @ 200 mA. Experimental results show that the peak efficiency is 91.8%. The input voltage ranges from 5 to 18 V, while a 2 A load current can be obtained. (paper)

  5. Microfabrication of a digital microfluidic platform integrated with an on-chip electrochemical cell

    We report on an IC compatible microfabrication process proposed for a novel monolithic lab-on-a-chip (LOC) with an electrochemical cell embedded in an electrowetting on dielectric (EWOD) digital microfluidic device. The optimized process focused on the surface modification of Teflon, selective exposure for the electrochemical module and recovery of surface properties by one-step annealing at low temperature. The optimum modification time and annealing temperature were 20 s and 210 °C, respectively. The experimental results from atomic force microscope and contact angle (CA) measurement revealed the effects of surface roughness and apparent CA on the wettability for different etch times. The multifunctionality of droplet creation, merger and transportation in the EWOD microfluidic module and sensitive electrochemical detection for the redox probe were realized simultaneously. The proposed microfabrication process has many advantages of remarkable simplicity, prominent repeatability, low cost and compatibility with standard IC processes. It shows great promise for the microsystem of the microfluidic unit and detecting cell, and gives a brilliant conception for the future fabrication of monolithic LOC integrated with functional detection. (paper)

  6. The fabrication of a double-layer atom chip with through silicon vias for an ultra-high-vacuum cell

    This study presents a double-layer atom chip that provides users with increased diversity in the design of the wire patterns and flexibility in the design of the magnetic field. It is more convenient for use in atomic physics experiments. A negative photoresist, SU-8, was used as the insulating layer between the upper and bottom copper wires. The electrical measurement results show that the upper and bottom wires with a width of 100 µm can sustain a 6 A current without burnout. Another focus of this study is the double-layer atom chips integrated with the through silicon via (TSV) technique, and anodically bonded to a Pyrex glass cell, which makes it a desired vacuum chamber for atomic physics experiments. Thus, the bonded glass cell not only significantly reduces the overall size of the ultra-high-vacuum (UHV) chamber but also conducts the high current from the backside to the front side of the atom chip via the TSV under UHV (9.5 × 10−10 Torr). The TSVs with a diameter of 70 µm were etched through by the inductively coupled plasma ion etching and filled by the bottom-up copper electroplating method. During the anodic bonding process, the electroplated copper wires and TSVs on atom chips also need to pass the examination of the required bonding temperature of 250 °C, under an applied voltage of 1000 V. Finally, the UHV test of the double-layer atom chips with TSVs at room temperature can be reached at 9.5 × 10−10 Torr, thus satisfying the requirements of atomic physics experiments under an UHV environment. (paper)

  7. In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip.

    Wu, Xuanye; Schneider, Nils; Platen, Alina; Mitra, Indranil; Blazek, Matthias; Zengerle, Roland; Schüle, Roland; Meier, Matthias


    Mammalian target of rapamycin (mTOR) is a central kinase integrating nutrient, energy, and metabolite signals. The kinase forms two distinct complexes: mTORC1 and mTORC2. mTORC1 plays an essential but undefined regulatory function for regeneration of adipose tissue. Analysis of mTOR in general is hampered by the complexity of regulatory mechanisms, including protein interactions and/or phosphorylation, in an ever-changing cellular microenvironment. Here, we developed a microfluidic large-scale integration chip platform for culturing and differentiating human adipose-derived stem cells (hASCs) in 128 separated microchambers under standardized nutrient conditions over 3 wk. The progression of the stem cell differentiation was measured by determining the lipid accumulation rates in hASC cultures. For in situ protein analytics, we developed a multiplex in situ proximity ligation assay (mPLA) that can detect mTOR in its two complexes selectively in single cells and implemented it on the same chip. With this combined technology, it was possible to reveal that the mTORC1 is regulated in its abundance, phosphorylation state, and localization in coordination with lysosomes during adipogenesis. High-content image analysis and parameterization of the in situ PLA signals in over 1 million cells cultured on four individual chips showed that mTORC1 and lysosomes are temporally and spatially coordinated but not in its composition during adipogenesis. PMID:27382182

  8. The development of an atom chip with through silicon vias for an ultra-high-vacuum cell

    This paper describes the development, fabrication and examination of an atom chip through silicon vias (TSV), which is anodically bonded with a Pyrex glass cell to form an ultra-high-vacuum system for the application of Bose–Einstein condensation (BEC) experiments. The silicon via is etched by the inductively coupled plasma reactive ion etch and filled by copper plating technology. The metal wires on both sides of the atom chips are patterned by the lithography process. Three different sizes of TSV are made and tested by continuously applying a maximum current of 17 A under the vacuum (70 Torr) and in air. In addition, after the thermal cycling of an anodic bonding process (requested at 350 °C) and a high electric field of 1000 V m−1, the TSV on atom chips can still hold the ultra-high vacuum (UHV). The conductive and vacuum yields of the TSV improved from 50% to 100% and from 75% to 81.25%, respectively after the modification of the fabrication process. Finally, the UHV test of TSV on atom chips at room temperature can be reached at 8 × 10−10 Torr, thus satisfying the requirements of atomic physics experiments under the UHV environment. (paper)

  9. On-chip test of the shift register for high-end network switch based on cell-based design

    Yamada, T.; Sekiya, A.; Akahori, A.; Akaike, H.; Fujimaki, A.; Hayakawa, H.; Kameda, Y.; Yorozu, S.; Terai, H.


    We have demonstrated the high-speed operation up to 55 GHz with a bias margin of +/-5.5% for a shift register based on the single-flux-quantum logic circuit. The shift register is employed in the rate transfer circuit in high-end network switches that are made up with the cell-based design technique. The on-chip test system was used for measuring the operation frequencies, and the test system itself was built by combining the cells to satisfy the boundary conditions between the test system and the circuit-under-test. As a result, the on-chip test system developed in this study has high flexibility.

  10. On-chip test of the shift register for high-end network switch based on cell-based design

    We have demonstrated the high-speed operation up to 55 GHz with a bias margin of ±5.5% for a shift register based on the single-flux-quantum logic circuit. The shift register is employed in the rate transfer circuit in high-end network switches that are made up with the cell-based design technique. The on-chip test system was used for measuring the operation frequencies, and the test system itself was built by combining the cells to satisfy the boundary conditions between the test system and the circuit-under-test. As a result, the on-chip test system developed in this study has high flexibility. (author)

  11. Microfluidics 3D gel-island chip for single cell isolation and lineage-dependent drug responses study.

    Zhang, Zhixiong; Chen, Yu-Chih; Cheng, Yu-Heng; Luan, Yi; Yoon, Euisik


    3D cell culture in the extracellular matrix (ECM), which not only provides structural support to cellular constituents, but also initiates regulatory biochemical cues for a variety of important cell functions in tissue, has become more and more important in understanding cancer pathology and drug testing. Although the ECM-gel has been used in cell culture both in bulk and on-chip, previous studies focused on collective cell behavior rather than single-cell heterogeneity. To track the behavior of each individual cell, we have developed a gel-island chip, which can form thousands of islands containing single cells encapsulated by the desired ECM. Optimized by Poisson's distribution, the device can attain 34% single cell capture efficiency of the exact number of single cells per island. A good culture media exchange rate and high cell viability can be achieved in the gel-islands. The cells in the islands can be automatically counted for high-throughput analysis. As a proof of concept, we monitored the proliferation and differentiation of single Notch+ (stem-like) T47D breast cancer cells. The 3D collagen gel environment was found to be favorable for the stem-like phenotype through better self-renewal and de-differentiation (Notch- to Notch+ transition). More interestingly, we found that the Notch- de-differentiated cells were more resistant to doxorubicin and cisplatin than the Notch+ cells. Combining the 3D ECM culture and single cell resolution, the presented platform can automatically analyze the individual cell behaviors of hundreds of cells using a small amount of drug and reagents. PMID:27270563

  12. Shielding analysis of the IEM cell offset adapter plate

    The adapter plate for the Interim Examination and Maintenance (IEM) cell ten foot ceiling valve was modified so that the penetration through the valve is offset to the north side of the steel plate. The modifications required that the shielding effectiveness be evaluated for several operating conditions. The highest gamma ray dose rate (51 mrem/hr) occurs when a Core Component Container (CCC) with six high burn-up driver fuel assemblies is transferred into or out of Solid Waste Cask (SWC). The neutron dose rate at the same source location is 2.5 mrem/hr. The total dose rate during the transfer is less than the 200 mrem/hr limit. If the ten foot ceiling valve is closed, the dose rate with twelve DFA in the cell will be less than 0.1 mrem/hr. However, with the ceiling valve open the dose rate will be as high as 12 mrem/hr. The latter condition will require controlled access to the area around the offset adapter plate when the ceiling valve is open. It was found that gaps in the shield block around the SWC floor valve will allow contact dose rates as high as 350 mrem/hr during the transfer of a fully loaded CCC. Although this situation does not pertain to the offset adapter plate, it will require controlled access around the SWC valve during the transfer of a fully loaded CCC

  13. Integrated potentiometric detector for use in chip-based flow cells

    Tantra; Manz


    A new kind of potentiometric chip sensor for ion-selective electrodes (ISE) based on a solvent polymeric membrane is described. The chip sensor is designed to trap the organic cocktail inside the chip and to permit sample solution to flow past the membrane. The design allows the sensor to overcome technical problems of ruggedness and would therefore be ideal for industrial processes. The sensor performance for a Ba2+-ISE membrane based on a Vogtle ionophore showed electrochemical behavior similar to that observed in conventional electrodes and microelectrode arrangements. PMID:10905321

  14. Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

    Jorgensen, Charles C.


    A Dynamic Cell Structure (DCS) Neural Network was developed which learns topology representing networks (TRNS) of F-15 aircraft aerodynamic stability and control derivatives. The network is integrated into a direct adaptive tracking controller. The combination produces a robust adaptive architecture capable of handling multiple accident and off- nominal flight scenarios. This paper describes the DCS network and modifications to the parameter estimation procedure. The work represents one step towards an integrated real-time reconfiguration control architecture for rapid prototyping of new aircraft designs. Performance was evaluated using three off-line benchmarks and on-line nonlinear Virtual Reality simulation. Flight control was evaluated under scenarios including differential stabilator lock, soft sensor failure, control and stability derivative variations, and air turbulence.

  15. Comparative evaluation of cell culture-adapted and chicken embryo-adapted fowl pox vaccine strains.

    Baxi, M K; Oberoi, M S


    Two types of vaccines, chicken embryo adapted (VacCE) and cell culture adapted (VacCC), were tested for their efficacy to elicite the immune response in birds vaccinated at 2 and 8 wk of age. The cell-mediated immune response studied by blastogenesis assay showed that birds vaccinated at the second week of age by both VacCE and VacCC vaccines had significant increase in T-lymphocyte count at 21 days postvaccination (PV) and 7 days postchallenge (PC), whereas in birds vaccinated at 8 wk of age, a significant increase was seen at 21 days PV and 7 days PC with the VacCC vaccine. The rise in passive hemagglutination titers was observed up to 21 days PV and 7 days PC in birds vaccinated at 2 wk of age. However, only the birds vaccinated with VacCC at 8 wk of age showed rise in titers at days 21 PV and 7 PC. Birds were challenged 90 days PV by scarification on the thigh region, and the birds vaccinated with VacCC showed 90% and 70% protection when vaccinated at 2 and 8 wk, respectively. The birds vaccinated with VacCE showed only 60% and 20% protection at the corresponding levels, respectively. PMID:10216755

  16. Acid stress adaptation protects saccharomyces cerevisiae from acetic acid-induced programme cell death

    Giannattasio, Sergio; Guaragnella, Nicoletta; Côrte-Real, Manuela; Passarella, Salvatore; Marra, Ersilia


    In this work evidence is presented that acid stress adaptation protects Saccharomyces cerevisiae from acetic acid-mediated programmed cell death. Exponential-phase yeast cells, non-adapted or adapted to acid stress by 30 min incubation in rich medium set at pH 3.0 with HCl, have been exposed to increasing concentrations of acetic acid and time course changes of cell viability have been assessed. Adapted cells, in contrast to non-adapted cells, when exposed to 80 mM acetic acid for 200 min ...

  17. A Low-Power and Low-Voltage Power Management Strategy for On-Chip Micro Solar Cells

    Ismail Cevik


    Full Text Available Fundamental characteristics of on-chip micro solar cell (MSC structures were investigated in this study. Several MSC structures using different layers in three different CMOS processes were designed and fabricated. Effects of PN junction structure and process technology on solar cell performance were measured. Parameters for low-power and low-voltage implementation of power management strategy and boost converter based circuits utilizing fractional voltage maximum power point tracking (FVMPPT algorithm were determined. The FVMPPT algorithm works based on the fraction between the maximum power point operation voltage and the open circuit voltage of the solar cell structure. This ratio is typically between 0.72 and 0.78 for commercially available poly crystalline silicon solar cells that produce several watts of power under typical daylight illumination. Measurements showed that the fractional voltage ratio is much higher and fairly constant between 0.82 and 0.85 for on-chip mono crystalline silicon micro solar cell structures that produce micro watts of power. Mono crystalline silicon solar cell structures were observed to result in better power fill factor (PFF that is higher than 74% indicating a higher energy harvesting efficiency.

  18. Adaptive Particle in Cell: Balanced Discretization and weighted Shape functions

    Geiser, Juergen; Schneider, Ralf; Matyash, Konstantin; Tskhakaya, David; Kalentyev, O


    In this paper we present a adaptive particle in cell method to extend the application to adaptive grid transformation and accelerate the solver process. The motivation arose of simulating near and fare-field application of plasma induced drive propulsion systems, called ion thruster. Here the problems of simulating a near-field in the drive propulsion system and the fare field of the shoot of the plasma particles of the system are hard and delicate to compute, see Birdsall 1985, Birdsall 1991. Based on the large scale computation of PIC codes, that can simulate up to $10^{10}$ particles, the accuracy of the particle solvers are very important. Due to the work of Tskhakaya et. al 2007, that allows only spatial symmetry and uniform grids, we propose a novel adaptive PIC method, that allows to use also non-uniform grids. Here, we have to balance the spatial symmetry to a spatial non-symmetry scheme, without loosing the physical correctness of conservation constraints. The results are discussed with numerical exp...

  19. Evaluation of in-plane local stress distribution in stacked IC chip using dynamic random access memory cell array for highly reliable three-dimensional IC

    Tanikawa, Seiya; Kino, Hisashi; Fukushima, Takafumi; Koyanagi, Mitsumasa; Tanaka, Tetsu


    As three-dimensional (3D) ICs have many advantages, IC performances can be enhanced without scaling down of transistor size. However, 3D IC has mechanical stresses inside Si substrates owing to its 3D stacking structure, which induces negative effects on transistor performances such as carrier mobility changes. One of the mechanical stresses is local bending stress due to organic adhesive shrinkage among stacked IC chips. In this paper, we have proposed an evaluation method for in-plane local stress distribution in the stacked IC chips using retention time modulation of a dynamic random access memory (DRAM) cell array. We fabricated a test structure composed of a DRAM chip bonded on a Si interposer with dummy Cu/Sn microbumps. As a result, we clarified that the DRAM cell array can precisely evaluate the in-plane local stress distribution in the stacked IC chips.

  20. Adaptive Response of T and B Cells in Atherosclerosis.

    Ketelhuth, Daniel F J; Hansson, Göran K


    Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease. PMID:26892965

  1. Nck adapter proteins: functional versatility in T cells

    Janssen Ottmar


    Full Text Available Abstract Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation.

  2. The effect of Cytochalasin D on F-Actin behavior of single-cell electroendocytosis using multi-chamber micro cell chip

    Lin, Ran


    Electroendocytosis (EED) is a pulsed-electric-field (PEF) induced endocytosis, facilitating cells uptake molecules through nanometer-sized EED vesicles. We herein investigate the effect of a chemical inhibitor, Cytochalasin D (CD) on the actin-filaments (F-Actin) behavior of single-cell EED. The CD concentration (C CD) can control the depolymerization of F-actin. A multi-chamber micro cell chip was fabricated to study the EED under different conditions. Large-scale single-cell data demonstrated EED highly depends on both electric field and C CD. © 2012 IEEE.

  3. High-throughput and clogging-free microfluidic filtration platform for on-chip cell separation from undiluted whole blood.

    Cheng, Yinuo; Ye, Xiongying; Ma, Zengshuai; Xie, Shuai; Wang, Wenhui


    Rapid separation of white blood cells from whole blood sample is often required for their subsequent analyses of functions and phenotypes, and many advances have been made in this field. However, most current microfiltration-based cell separation microfluidic chips still suffer from low-throughput and membrane clogging. This paper reports on a high-throughput and clogging-free microfluidic filtration platform, which features with an integrated bidirectional micropump and commercially available polycarbonate microporous membranes. The integrated bidirectional micropump enables the fluid to flush micropores back and forth, effectively avoiding membrane clogging. The microporous membrane allows red blood cells passing through high-density pores in a cross-flow mixed with dead-end filtration mode. All the separation processes, including blood and buffer loading, separation, and sample collection, are automatically controlled for easy operation and high throughput. Both microbead mixture and undiluted whole blood sample are separated by the platform effectively. In particular, for white blood cell separation, the chip recovered 72.1% white blood cells with an over 232-fold enrichment ratio at a throughput as high as 37.5 μl/min. This high-throughput, clogging-free, and highly integrated platform holds great promise for point-of-care blood pretreatment, analysis, and diagnosis applications. PMID:26909124

  4. Excimer laser micropatterning of freestanding thermo-responsive hydrogel layers for cells-on-chip applications

    We report a novel reliable and repeatable technologic manufacturing protocol for the realization of micro-patterned freestanding hydrogel layers based on thermo-responsive poly-(N-isopropyl)acrylamide (PNIPAAm), which have potential to be employed as temperature-triggered smart surfaces for cells-on-chip applications. PNIPAAm-based films with controlled mechanical properties and different thicknesses (100–300 µm thickness) were prepared by injection compression moulding at room temperature. A 9 × 9 array of 20 µm diameter through-holes is machined by means of the KrF excimer laser on dry PNIPAAm films which are physically attached to flat polyvinyl chloride (PVC) substrates. Machining parameters, such as fluence and number of shots, are optimized in order to achieve highly resolved features. Micro-structured freestanding films are then easily obtained after hydrogels are detached from PVC by gradually promoting the film swelling in ethanol. In the PNIPAAm water-swollen state, the machined holes’ diameter approaches a slight larger value (30 µm) according to the measured hydrogel swelling ratio. Thermo-responsive behaviour and through-hole tapering characterization are carried out by metrology measurements using an optical inverted and confocal microscope setup, respectively. After the temperature of freestanding films is raised above 32 °C, we observe that the shrinkage of the whole through-hole array occurs, thus reducing the holes’ diameter to less than a half its original size (about 15 µm) as a consequence of the film dehydration. Different holes’ diameters (10 and 30 µm) are also obtained on dry hydrogel employing suitable projection masks, showing similar shrinking behaviour when hydrated and undergone thermo-response tests. Thermo-responsive PNIPAAm-based freestanding layers could then be integrated with other suitable micro-fabricated thermoplastic components in order to preliminary test their feasibility in operating as temperature

  5. On-chip fabrication of alkali-metal vapor cells utilizing an alkali-metal source tablet

    We describe a novel on-chip microfabrication technique for the alkali-metal vapor cell of an optically pumped atomic magnetometer (OPAM), utilizing an alkali-metal source tablet (AMST). The newly proposed AMST is a millimeter-sized piece of porous alumina whose considerable surface area holds deposited alkali-metal chloride (KCl) and barium azide (BaN6), source materials that effectively produce alkali-metal vapor at less than 400 °C. Our experiments indicated that the most effective pore size of the AMST is between 60 and 170 µm. The thickness of an insulating glass spacer holding the AMST was designed to confine generated alkali metal to the interior of the vapor cell during its production, and an integrated silicon heater was designed to seal the device using a glass frit, melted at an optimum temperature range of 460–490 °C that was determined by finite element method thermal simulation. The proposed design and AMST were used to successfully fabricate a K cell that was then operated as an OPAM with a measured sensitivity of 50 pT. These results demonstrate that the proposed concept for on-chip microfabrication of alkali-metal vapor cells may lead to effective replacement of conventional glassworking approaches. (paper)

  6. Very High Throughput Electrical Cell Lysis and Extraction of Intracellular Compounds Using 3D Carbon Electrodes in Lab-on-a-Chip Devices

    Philippe Renaud


    Full Text Available Here we present an electrical lysis throughput of 600 microliters per minute at high cell density (108 yeast cells per ml with 90% efficiency, thus improving the current common throughput of one microliter per minute. We also demonstrate the extraction of intracellular luciferase from mammalian cells with efficiency comparable to off-chip bulk chemical lysis. The goal of this work is to develop a sample preparation module that can act as a stand-alone device or be integrated to other functions already demonstrated in miniaturized devices, including sorting and analysis, towards a true lab-on-a-chip.

  7. Evidence that Cell Death is Associated with Zebra Chip Disease in Potato Tubers

    Zebra chip (ZC) is an established and highly destructive disease of potato (Solanum tuberosum L.) that occurs in several southwestern states of the United States, Mexico, Central America, and New Zealand. The causal agent for this disease has not been identified. However, the bacterium ‘Candidatus ...

  8. Adapt

    Bargatze, L. F.


    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  9. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

    Butler, A. E.; Cao-Minh, L.; Galasso, R; Rizza, R. A.; Corradin, A.; Cobelli, C; Butler, P C


    Aims/hypothesis We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy. Methods Pancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cel...

  10. Stiffness-Independent Highly Efficient On-Chip Extraction of Cell-Laden Hydrogel Microcapsules from Oil Emulsion into Aqueous Solution by Dielectrophoresis.

    Huang, Haishui; Sun, Mingrui; Heisler-Taylor, Tyler; Kiourti, Asimina; Volakis, John; Lafyatis, Gregory; He, Xiaoming


    A dielectrophoresis (DEP)-based method achieves highly efficient on-chip extraction of cell-laden microcapsules of any stiffness from oil into aqueous solution. The hydrogel microcapsules can be extracted into the aqueous solution by DEP and interfacial tension forces with no trapped oil, while the encapsulated cells are free from electrical damage due to the Faraday cage effect. PMID:26297051

  11. Experiment list: SRX367328 [Chip-atlas[Archive

    Full Text Available nology) || sirna transfection=siCTL cell || cell line=Human Embryonic Kidney 293 cells || chip antibody=CDK9 || chip antibody details=2316S (Cell Signaling Tech

  12. Experiment list: SRX367330 [Chip-atlas[Archive

    Full Text Available nology) || sirna transfection=siBrd4 cell || cell line=Human Embryonic Kidney 293 cells || chip antibody=CDK9 || chip antibody details=2316S (Cell Signaling Tech

  13. Experiment list: SRX367329 [Chip-atlas[Archive

    Full Text Available hnology) || sirna transfection=siJMJD6 http://dbarchive....e=HEK293T cell || cell line=Human Embryonic Kidney 293 cells || chip antibody=CDK9 || chip antibody details=2316S (Cell Signaling Tec

  14. Hidden talents of natural killers: NK cells in innate and adaptive immunity

    Cooper, Megan A.; Colonna, Marco; Yokoyama, Wayne M.


    Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells and producing immunoregulatory cytokines. Herein, we discuss recent studies that indicate that NK cells span the conventional boundaries between innate and adaptive immunity. For example, it was recently discovered that NK cells have the capacity for memory-like responses, a property that was previously thought to be limited to adaptive immunity. NK cells have also been identified in multiple tissues, and ...

  15. Strategies for adaptation of mAb-producing CHO cells to serum-free medium

    Costa A; Rodrigues M.; Henriques Mariana; Oliveira Rosário; Azeredo Joana


    Large-scale production of biopharmaceuticals commonly requires the use of serum-free medium, for safety and cost reasons. However, serum is essential to most mammalian cells growth, and its removal implies a very time-consuming process for cell adaptation. Thus, the aim of the study was to evaluate different strategies for cell adaptation to serum-free medium. Three cell types were used to assess the impact of transfection on adaptation: one common CHO-K1 cell line and two CHO-K1 cells tr...

  16. A population dynamics analysis of the interaction between adaptive regulatory T cells and antigen presenting cells.

    David Fouchet

    Full Text Available BACKGROUND: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. METHODOLOGY AND PRINCIPAL FINDINGS: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. CONCLUSION/SIGNIFICANCE: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens.

  17. Atom chips

    Reichel, Jakob


    This book provides a stimulating and multifaceted picture of a rapidly developing field. The first part reviews fundamentals of atom chip research in tutorial style, while subsequent parts focus on the topics of atom-surface interaction, coherence on atom chips, and possible future directions of atom chip research. The articles are written by leading researchers in the field in their characteristic and individual styles.

  18. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  19. Mechanism of action of cis-dichloro-bis (isopropylamine) trans dihydroxyplatinum IV (CHIP) on Chinese hamster and C3H mouse tumor cells and its interaction with x-irradiation

    CHIP acts as a hypoxic cell sensitizer when used in conjunction with x-irradiation. A change in the extrapolation number of the radiation survival curve of Chinese hamster ovary (CHO) cells is observed but the exponential slope (D0) remains the same. Chinese hamster ovary cells appear to be less sensitive than C3H mouse mammary tumor cells to CHIP. The type and level of chromosome aberrations observed in CHO cells indicate that the mechanism of action of CHIP is similar to that seen with bifunctional alkylating agents

  20. A chip-type thin-layer electrochemical cell coupled with capillary electrophoresis for online separation of electrode reaction products

    He, Jian-Bo, E-mail:; Cui, Ting; Zhang, Wen-Wen; Deng, Ning


    Graphical abstract: -- Highlights: •A new coupling of thin-layer electrolysis with capillary electrophoresis (CE). •Rapid electrolysis, direct sampling followed by online CE separation. •At least 13 products of quercetin oxidation were separated. •Thermodynamic and kinetic parameters were determined from CE peak areas. -- Abstract: A coupling technique of thin-layer electrolysis with high-performance capillary electrophoresis/UV–vis technique(EC/HPCE/UV–vis) is developed for online separation and determination of electrode reaction products. A chip-type thin-layer electrolytic (CTE) cell was designed and fabricated, which contains a capillary channel and a background electrolyte reservoir, allowing rapid electrolysis, direct sampling and online electrophoretic separation. This chip-type setup was characterized based on an electrophoresis expression of Nernst equation that was applied to the redox equilibrium of o-tolidine at different potentials. The utility of the method was demonstrated by separating and determining the electro-oxidation products of quercetin in different pH media. Two main products were always found in the studied time, potential and pH ranges. The variety of products increased not only with increasing potential but also with increasing pH value, and in total, at least 13 products were observed in the electropherograms. This work illustrates a novel example of capillary electrophoresis used online with thin-layer electrolysis to separate and detect electrode reaction products.

  1. A chip-type thin-layer electrochemical cell coupled with capillary electrophoresis for online separation of electrode reaction products

    Graphical abstract: -- Highlights: •A new coupling of thin-layer electrolysis with capillary electrophoresis (CE). •Rapid electrolysis, direct sampling followed by online CE separation. •At least 13 products of quercetin oxidation were separated. •Thermodynamic and kinetic parameters were determined from CE peak areas. -- Abstract: A coupling technique of thin-layer electrolysis with high-performance capillary electrophoresis/UV–vis technique(EC/HPCE/UV–vis) is developed for online separation and determination of electrode reaction products. A chip-type thin-layer electrolytic (CTE) cell was designed and fabricated, which contains a capillary channel and a background electrolyte reservoir, allowing rapid electrolysis, direct sampling and online electrophoretic separation. This chip-type setup was characterized based on an electrophoresis expression of Nernst equation that was applied to the redox equilibrium of o-tolidine at different potentials. The utility of the method was demonstrated by separating and determining the electro-oxidation products of quercetin in different pH media. Two main products were always found in the studied time, potential and pH ranges. The variety of products increased not only with increasing potential but also with increasing pH value, and in total, at least 13 products were observed in the electropherograms. This work illustrates a novel example of capillary electrophoresis used online with thin-layer electrolysis to separate and detect electrode reaction products

  2. Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform.

    Josefina Dykes

    Full Text Available BACKGROUND: Excessive collection of platelets is an unwanted side effect in current centrifugation-based peripheral blood progenitor cell (PBPC apheresis. We investigated a novel microchip-based acoustophoresis technique, utilizing ultrasonic standing wave forces for the removal of platelets from PBPC products. By applying an acoustic standing wave field onto a continuously flowing cell suspension in a micro channel, cells can be separated from the surrounding media depending on their physical properties. STUDY DESIGN AND METHODS: PBPC samples were obtained from patients (n = 15 and healthy donors (n = 6 and sorted on an acoustophoresis-chip. The acoustic force was set to separate leukocytes from platelets into a target fraction and a waste fraction, respectively. The PBPC samples, the target and the waste fractions were analysed for cell recovery, purity and functionality. RESULTS: The median separation efficiency of leukocytes to the target fraction was 98% whereas platelets were effectively depleted by 89%. PBPC samples and corresponding target fractions were similar in the percentage of CD34+ hematopoetic progenitor/stem cells as well as leukocyte/lymphocyte subset distributions. Median viability was 98%, 98% and 97% in the PBPC samples, the target and the waste fractions, respectively. Results from hematopoietic progenitor cell assays indicated a preserved colony-forming ability post-sorting. Evaluation of platelet activation by P-selectin (CD62P expression revealed a significant increase of CD62P+ platelets in the target (19% and waste fractions (20%, respectively, compared to the PBPC input samples (9%. However, activation was lower when compared to stored blood bank platelet concentrates (48%. CONCLUSION: Acoustophoresis can be utilized to efficiently deplete PBPC samples of platelets, whilst preserving the target stem/progenitor cell and leukocyte cell populations, cell viability and progenitor cell colony-forming ability

  3. Gene expression profile differences in high and low metastatic human ovarian cancer cell lines by gene chip

    许沈华; 牟瀚舟; 吕桂泉; 朱赤红; 羊正炎; 高永良; 楼洪坤; 刘祥麟; 程勇; 杨文


    Objectives To study the difference between gene expressions of high (H0-8910PM) and low (HO-8910) metastatic human ovarian carcinoma cell lines and screen novel associated genes by cDNA microarray. Methods cDNA retro-transcribed from equal quantities of mRNA derived from high and low metastatic tumor cells or normal ovarian tissues were labeled with Cy5 and Cy3 fluorescein as probes. The mixed probe was hybridized with two pieces of BioDoor 4096 double dot human whole gene chip and scanned with a ScanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results A total of 355 genes with expression levels more than 3 times larger were found by comparing the HO-8910 cell with normal ovarian epithelial cells. A total of 323 genes with expression levels more than 3 times larger in HO-8910PM cells compared to normal ovarian epithelium cells were also detected. A total of 165 genes whose expression levels were more than two times those of HO-8910PM cells compared to their mother cell line (HO-8910) were detected. Twenty-one genes with expression levels >3 times were found from comparison of these two tumor cell lines.Conclusions cDNA microarray techniques are effective in screening differential gene expression between two human ovarian cancer cell lines (H0-8910PM; HO-8910) and normal ovarian epithelial cells. These genes may be related to the genesis and development of ovarian carcinoma. Analysis of the human ovarian cancer gene expression profile with cDNA microarray may help in gene diagnosis, treatment and prevention.

  4. Design, Fabrication and Prototype testing of a Chip Integrated Micro PEM Fuel Cell Accumulator combined On-Board Range Extender

    In this work we present the design, fabrication and prototype testing of Chip Integrated Micro PEM Fuel Cell Accumulator (CIμ-PFCA) combined On-Board Range Extender (O-BRE). CIμ-PFCA is silicon based micro-PEM fuel cell system with an integrated hydrogen storage feature (palladium metal hydride), the run time of CIμ-PFCA is dependent on the stored hydrogen, and in order to extend its run time an O-BRE is realized (catalytic hydrolysis of chemical hydride, NaBH4. Combining the CIμ-PFCA and O-BRE on a system level have few important design requirements to be considered; hydrogen regulation, gas -liquid separator between the CIμ-PFCA and the O-RE. The usage of traditional techniques to regulate hydrogen (tubes), gas-liquid phase membranes (porous membrane separators) are less desirable in the micro domain, due to its space constraint. Our approach is to use a passive hydrogen regulation and gas-liquid phase separation concept; to use palladium membrane. Palladium regulates hydrogen by concentration diffusion, and its property to selectively adsorb only hydrogen is used as a passive gas-liquid phase separator. Proof of concept is shown by realizing a prototype system. The system is an assembly of CIμ-PFCA, palladium membrane and the O-BRE. The CIμ-PFCA consist of 2 individually processed silicon chips, copper supported palladium membrane realized by electroplating followed by high temperature annealing process under inter atmosphere and the O-BRE is realized out of a polymer substrate by micromilling process with platinum coated structures, which functions as a catalyst for the hydrolysis of NaBH4. The functionality of the assembled prototype system is demonstrated by the measuring a unit cell (area 1 mm2) when driven by the catalytic hydrolysis of chemical hydride (NaBH4 and the prototype system shows run time more than 15 hours

  5. A Method to Study the Epigenetic Chromatin States of Rare Hematopoietic Stem and Progenitor Cells; MiniChIP–Chip

    Weishaupt Holger


    Full Text Available Abstract Dynamic chromatin structure is a fundamental property of gene transcriptional regulation, and has emerged as a critical modulator of physiological processes during cellular differentiation and development. Analysis of chromatin structure using molecular biology and biochemical assays in rare somatic stem and progenitor cells is key for understanding these processes but poses a great challenge because of their reliance on millions of cells. Through the development of a miniaturized genome-scale chromatin immunoprecipitation method (miniChIP–chip, we have documented the genome-wide chromatin states of low abundant populations that comprise hematopoietic stem cells and immediate progeny residing in murine bone marrow. In this report, we describe the miniChIP methodology that can be used for increasing an understanding of the epigenetic mechanisms underlying hematopoietic stem and progenitor cell function. Application of this method will reveal the contribution of dynamic chromatin structure in regulating the function of other somatic stem cell populations, and how this process becomes perturbed in pathological conditions. Additional file 1 Click here for file

  6. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail:, E-mail: [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)


    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  7. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  8. Use of an adaptable cell culture kit for performing lymphocyte and monocyte cell cultures in microgravity

    Hatton, J. P.; Lewis, M. L.; Roquefeuil, S. B.; Chaput, D.; Cazenave, J. P.; Schmitt, D. A.


    -based investigations simulating the conditions expected in the flight experiment. Several parameters including cell concentration, time between cell loading and activation, and storage temperature on cell survival were examined to characterise cell response and optimise the experiments to be flown aboard the Space Shuttle. Results indicate that the objectives of the experiments could be met with delays up to 5 days between cell loading into the hardware and initial in flight experiment activation, without the need for medium exchange. Experiment hardware of this kind, which is adaptable to a wide range of cell types and can be easily interfaced to different spacecraft facilities, offers the possibility for a wide range of experimenters successfully and easily to utilise future flight opportunities.

  9. Function projective synchronization of two-cell quantum-CNN chaotic oscillators by nonlinear adaptive controller

    In this Letter, we investigate function projective synchronization of two-cell quantum-CNN chaotic oscillators using nonlinear adaptive controller. Based on Lyapunov stability theory, the nonlinear adaptive control law is derived to make the state of two chaotic systems function projective synchronized. Two numerical simulations are presented to illustrate the effectiveness of the proposed nonlinear adaptive control scheme, which is more effective than that in previous literature.

  10. Adaptive function projective synchronization of two-cell Quantum-CNN chaotic oscillators with uncertain parameters

    This work investigates function projective synchronization of two-cell Quantum-CNN chaotic oscillators using adaptive method. Quantum-CNN oscillators produce nano scale chaotic oscillations under certain conditions. By Lyapunove stability theory, the adaptive control law and the parameter update law are derived to make the state of two chaotic systems function projective synchronized. Numerical simulations are presented to demonstrate the effectiveness of the proposed adaptive controllers.

  11. Stochastic adaptation and fold-change detection: from single-cell to population behavior

    Leier André


    Full Text Available Abstract Background In cell signaling terminology, adaptation refers to a system's capability of returning to its equilibrium upon a transient response. To achieve this, a network has to be both sensitive and precise. Namely, the system must display a significant output response upon stimulation, and later on return to pre-stimulation levels. If the system settles at the exact same equilibrium, adaptation is said to be 'perfect'. Examples of adaptation mechanisms include temperature regulation, calcium regulation and bacterial chemotaxis. Results We present models of the simplest adaptation architecture, a two-state protein system, in a stochastic setting. Furthermore, we consider differences between individual and collective adaptive behavior, and show how our system displays fold-change detection properties. Our analysis and simulations highlight why adaptation needs to be understood in terms of probability, and not in strict numbers of molecules. Most importantly, selection of appropriate parameters in this simple linear setting may yield populations of cells displaying adaptation, while single cells do not. Conclusions Single cell behavior cannot be inferred from population measurements and, sometimes, collective behavior cannot be determined from the individuals. By consequence, adaptation can many times be considered a purely emergent property of the collective system. This is a clear example where biological ergodicity cannot be assumed, just as is also the case when cell replication rates are not homogeneous, or depend on the cell state. Our analysis shows, for the first time, how ergodicity cannot be taken for granted in simple linear examples either. The latter holds even when cells are considered isolated and devoid of replication capabilities (cell-cycle arrested. We also show how a simple linear adaptation scheme displays fold-change detection properties, and how rupture of ergodicity prevails in scenarios where transitions between

  12. A chip assisted immunomagnetic separation system for the efficient capture and in situ identification of circulating tumor cells.

    Tang, Man; Wen, Cong-Ying; Wu, Ling-Ling; Hong, Shao-Li; Hu, Jiao; Xu, Chun-Miao; Pang, Dai-Wen; Zhang, Zhi-Ling


    The detection of circulating tumor cells (CTCs), a kind of "liquid biopsy", represents a potential alternative to noninvasive detection, characterization and monitoring of carcinoma. Many previous studies have shown that the number of CTCs has a significant relationship with the stage of cancer. However, CTC enrichment and detection remain notoriously difficult because they are extremely rare in the bloodstream. Herein, aided by a microfluidic device, an immunomagnetic separation system was applied to efficiently capture and in situ identify circulating tumor cells. Magnetic nanospheres (MNs) were modified with an anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody to fabricate immunomagnetic nanospheres (IMNs). IMNs were then loaded into the magnetic field controllable microfluidic chip to form uniform IMN patterns. The IMN patterns maintained good stability during the whole processes including enrichment, washing and identification. Apart from its simple manufacture process, the obtained microfluidic device was capable of capturing CTCs from the bloodstream with an efficiency higher than 94%. The captured cells could be directly visualized with an inverted fluorescence microscope in situ by immunocytochemistry (ICC) identification, which decreased cell loss effectively. Besides that, the CTCs could be recovered completely just by PBS washing after removal of the permanent magnets. It was observed that all the processes showed negligible influence on cell viability (viability up to 93%) and that the captured cells could be re-cultured for more than 5 passages after release without disassociating IMNs. In addition, the device was applied to clinical samples and almost all the samples from patients showed positive results, which suggests it could serve as a valuable tool for CTC enrichment and detection in the clinic. PMID:26928405

  13. Analysis of TNF-α-induced Leukocyte Adhesion to Vascular Endothelial Cells Regulated by Fluid Shear Stress Using Microfluidic Chip-based Technology

    LI Yuan; YANG De-yu; LIAO Juan; GONG Fang; HE Ping; LIU Bei-zhong


    This paper aims to the research of the impact of fluid shear stress on the adhesion between vascular endothelial cells and leukocyte induced by tumor necrosis factor-α(TNF-α) by microfliudic chip technology. Microfluidic chip was fabricated by soft lithograph;Endothelial microfluidic chip was constructed by optimizing types of the extracellular matrix proteins modified in the microchannel and cell incubation time;human umbilical vein endothelial cells EA.Hy926 lined in the microchannel were exposed to fluid shear stress of 1.68 dynes/cm2 and 8.4 dynes/cm2 respectively. Meanwhile, adhesion between EA.Hy926 cells and leukocyte was induced by TNF-αunder a flow condition. EA. Hy926 cell cultured in the static condition was used as control group. The numbers of fluorescently-labeled leukocyte in microchannel were counted to quantize the adhesion level between EA. Hy926 cells and leukocyte; cell immunofluorescence technique was used to detect the intercellular adhesion molecule (ICAM-1) expression. The constructed endothelial microfluidic chip can afford to the fluid shear stress and respond to exogenous stimulus of TNF-α;compared with the adhesion numbers of leukocyte in control group, adhesion between EA. Hy926 cells exposed to low fluid shear stress and leukocyte was reduced under the stimulus of TNF-α at a concentration of 10 ng/ml(P<0.05);leukocyte adhesion with EA. Hy926 cells exposed to high fluid shear stress was reduced significantly than EA. Hy926 cells in control group and EA.1Hy926 cells exposed to low fluid shear stress ( P<0.01); the regulation mechanism of fluid shear stress to the adhesion between EA. Hy926 cells and leukocyte induced by TNF-αwas through the way of ICAM-1. The endothelial microfluidic chip fabricated in this paper could be used to study the functions of endothelial cell in vitro and provide a new technical platform for exploring the pathophysiology of the related cardiovascular system diseases under a flow environment.

  14. File list: DNS.CDV.50.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available DNS.CDV.50.AllAg.Endocardial_cells hg19 DNase-seq Cardiovascular Endocardial cells ... ...

  15. File list: His.CDV.20.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available His.CDV.20.AllAg.Endocardial_cells hg19 Histone Cardiovascular Endocardial cells ...

  16. File list: DNS.CDV.05.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available DNS.CDV.05.AllAg.Endocardial_cells hg19 DNase-seq Cardiovascular Endocardial cells ... ...

  17. File list: His.CDV.10.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available His.CDV.10.AllAg.Endocardial_cells hg19 Histone Cardiovascular Endocardial cells ...

  18. File list: Unc.CDV.05.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available Unc.CDV.05.AllAg.Endocardial_cells hg19 Unclassified Cardiovascular Endocardial ...

  19. File list: DNS.CDV.10.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available DNS.CDV.10.AllAg.Endocardial_cells hg19 DNase-seq Cardiovascular Endocardial cells ... ...

  20. File list: Unc.PSC.10.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.PSC.10.Unclassified.AllCell mm9 Unclassified Unclassified Pluripotent stem cell...25,SRX213761 ...

  1. File list: Unc.PSC.50.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.PSC.50.Unclassified.AllCell mm9 Unclassified Unclassified Pluripotent stem cell...73,SRX355578 ...

  2. File list: Unc.CDV.20.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available Unc.CDV.20.AllAg.Endocardial_cells hg19 Unclassified Cardiovascular Endocardial ...

  3. File list: Unc.CDV.50.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available Unc.CDV.50.AllAg.Endocardial_cells hg19 Unclassified Cardiovascular Endocardial ...

  4. File list: DNS.CDV.20.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available DNS.CDV.20.AllAg.Endocardial_cells hg19 DNase-seq Cardiovascular Endocardial cells ... ...

  5. File list: His.CDV.50.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available His.CDV.50.AllAg.Endocardial_cells hg19 Histone Cardiovascular Endocardial cells ...

  6. File list: His.CDV.05.AllAg.Endocardial_cells [Chip-atlas[Archive

    Full Text Available His.CDV.05.AllAg.Endocardial_cells hg19 Histone Cardiovascular Endocardial cells ...

  7. Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models

    Li, Encheng; Xu, Zhiyun; Zhao, Hui; Sun, Zhao; Wang, Lei; Guo, Zhe; Zhao, Yang; GAO, ZHANCHENG; Wang, Qi


    We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation...

  8. File list: DNS.Prs.10.AllAg.Prostate_cancer_cells [Chip-atlas[Archive

    Full Text Available DNS.Prs.10.AllAg.Prostate_cancer_cells hg19 DNase-seq Prostate Prostate cancer cell...s ...

  9. File list: ALL.PSC.05.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.05.AllAg.iPS_cells mm9 All antigens Pluripotent stem cell iPS cells SRX9774...30,SRX146524,SRX146522,SRX146547 ...

  10. File list: ALL.PSC.10.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.10.AllAg.iPS_cells hg19 All antigens Pluripotent stem cell iPS cells SRX753...09,SRX189400,SRX189399 ...

  11. File list: Oth.PSC.10.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available Oth.PSC.10.AllAg.iPS_cells mm9 TFs and others Pluripotent stem cell iPS cells SRX65...RX146524 ...

  12. File list: DNS.PSC.10.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available DNS.PSC.10.AllAg.iPS_cells hg19 DNase-seq Pluripotent stem cell iPS cells SRX040379...,SRX040378,SRX040377,SRX040376,SRX135563,SRX189427,SRX189400,SRX189399 ...

  13. File list: ALL.PSC.20.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.20.AllAg.iPS_cells hg19 All antigens Pluripotent stem cell iPS cells SRX088...27,SRX189400,SRX189399 ...

  14. File list: His.PSC.10.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available His.PSC.10.AllAg.iPS_cells mm9 Histone Pluripotent stem cell iPS cells SRX977417,SR...RX127372,SRX1090869,SRX127376,SRX035977,SRX146530,SRX146547,SRX146522 ...

  15. File list: Oth.PSC.50.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available Oth.PSC.50.AllAg.iPS_cells mm9 TFs and others Pluripotent stem cell iPS cells SRX97...RX146524 ...

  16. File list: DNS.PSC.05.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available DNS.PSC.05.AllAg.iPS_cells hg19 DNase-seq Pluripotent stem cell iPS cells SRX040379...,SRX040378,SRX040377,SRX040376,SRX135563,SRX189427,SRX189400,SRX189399 ...

  17. File list: His.PSC.10.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available His.PSC.10.AllAg.iPS_cells hg19 Histone Pluripotent stem cell iPS cells SRX110016,S...315,SRX381309 ...

  18. File list: ALL.PSC.10.AllAg.STAP_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.10.AllAg.STAP_cells mm9 All antigens Pluripotent stem cell STAP cells SRX47...2660,SRX472654,SRX472663,SRX472665,SRX472656,SRX472662,SRX472661,SRX472664,SRX472655 ...

  19. File list: His.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Full Text Available His.Utr.20.AllAg.Ovarian_granulosa_cells hg19 Histone Uterus Ovarian granulosa cell...s ...

  20. File list: His.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Full Text Available His.Utr.05.AllAg.Ovarian_granulosa_cells hg19 Histone Uterus Ovarian granulosa cell...s ...

  1. File list: His.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Full Text Available His.Utr.10.AllAg.Ovarian_granulosa_cells hg19 Histone Uterus Ovarian granulosa cell...s ...

  2. File list: His.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Full Text Available His.Utr.50.AllAg.Ovarian_granulosa_cells hg19 Histone Uterus Ovarian granulosa cell...s ...

  3. File list: His.Gon.20.AllAg.Testicular_somatic_cells [Chip-atlas[Archive

    Full Text Available His.Gon.20.AllAg.Testicular_somatic_cells mm9 Histone Gonad Testicular somatic cell...s SRX591729,SRX591717 ...

  4. File list: ALL.PSC.05.AllAg.STAP_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.05.AllAg.STAP_cells mm9 All antigens Pluripotent stem cell STAP cells SRX47...2660,SRX472663,SRX472654,SRX472665,SRX472656,SRX472662,SRX472661,SRX472664,SRX472655 ...

  5. File list: Pol.PSC.20.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available Pol.PSC.20.AllAg.iPS_cells mm9 RNA polymerase Pluripotent stem cell iPS cells SRX97...7435,SRX977434,SRX027462 ...

  6. File list: Oth.PSC.05.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available Oth.PSC.05.AllAg.iPS_cells mm9 TFs and others Pluripotent stem cell iPS cells SRX65...RX146524 ...

  7. File list: DNS.PSC.50.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available DNS.PSC.50.AllAg.iPS_cells hg19 DNase-seq Pluripotent stem cell iPS cells SRX040379...,SRX040378,SRX135563,SRX040376,SRX040377,SRX189427,SRX189400,SRX189399 ...

  8. File list: ALL.PSC.20.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.20.AllAg.iPS_cells mm9 All antigens Pluripotent stem cell iPS cells SRX9773...30,SRX146522,SRX146547 ...

  9. File list: ALL.PSC.50.AllAg.iPS_cells [Chip-atlas[Archive

    Full Text Available ALL.PSC.50.AllAg.iPS_cells mm9 All antigens Pluripotent stem cell iPS cells SRX9773...1,SRX035985,SRX1090869 ...


    WU Peining; TAN Jianrong; LIU Zhenyu


    Adaptive layered Cartesian cut cell method is presented to solve the difficulty of the unstructured hexahedral anisotropic Cartesian grids generation from the complex CAD model. Vertex merging algorithm based on relaxed AVL tree is investigated to construct topological structure for stereo lithography (STL) files, and a topology-based self-adaptive layered slicing algorithm with special features control strategy is brought forward. With the help of convex hull, a new points-in-polygon method is employed to improve the Cartesian cut cell method. By integrating the self-adaptive layered slicing algorithm and the improved Cartesian cut cell method, the adaptive layered Cartesian cut cell method gains the volume data of the complex CAD model in STL file and generates the unstructured hexahedral anisotropic Cartesian grids.

  11. A Robot-Assisted Cell Manipulation System with an Adaptive Visual Servoing Method

    Yu Xie; Feng Zeng; Wenming Xi; Yunlei Zhou; Houde Liu; Mingliang Chen


    Robot-assisted cell manipulation is gaining attention for its ability in providing high throughput and high precision cell manipulation for the biological industry. This paper presents a visual servo microrobotic system for cell microinjection. We investigated the automatic cell autofocus method that reduced the complexity of the system. Then, we produced an adaptive visual processing algorithm to detect the location of the cell and micropipette toward the uneven illumination problem. Fourtee...

  12. Temperature gradient stimulation for cell division in C. Elegans Embryos on chip

    Baranek, Sophie; Bezler, Alexandra; Adamczyk, Christian; Gönczy, Pierre; Renaud, Philippe


    This paper reports on a new microfluidic device for temperature stimulation of cell in in-vitro culture. Micro-electrodes in a meander shape are embedded into the microfluidic channels to generate either a temperature gradient through the culture chamber or a local heat spot under specific cells. One promising application is the control of cell di- vision rate. Here we present first results of the synchronization of cell division in a two-cell stage embryos of C. Elegans.

  13. New method for selection of hydrogen peroxide adapted bifidobacteria cells using continuous culture and immobilized cell technology

    Meile Leo


    Full Text Available Abstract Background Oxidative stress can severely compromise viability of bifidobacteria. Exposure of Bifidobacterium cells to oxygen causes accumulation of reactive oxygen species, mainly hydrogen peroxide, leading to cell death. In this study, we tested the suitability of continuous culture under increasing selective pressure combined with immobilized cell technology for the selection of hydrogen peroxide adapted Bifidobacterium cells. Cells of B. longum NCC2705 were immobilized in gellan-xanthan gum gel beads and used to continuously ferment MRS medium containing increasing concentration of H2O2 from 0 to 130 ppm. Results At the beginning of the culture, high cell density of 1013 CFU per litre of reactor was tested. The continuous culture gradually adapted to increasing H2O2 concentrations. However, after increasing the H2O2 concentration to 130 ppm the OD of the culture decreased to 0. Full wash out was prevented by the immobilization of the cells in gel matrix. Hence after stopping the stress, it was possible to re-grow the cells that survived the highest lethal dose of H2O2 and to select two adapted colonies (HPR1 and HPR2 after plating of the culture effluent. In contrast to HPR1, HPR2 showed stable characteristics over at least 70 generations and exhibited also higher tolerance to O2 than non adapted wild type cells. Preliminary characterization of HPR2 was carried out by global genome expression profile analysis. Two genes coding for a protein with unknown function and possessing trans-membrane domains and an ABC-type transporter protein were overexpressed in HPR2 cells compared to wild type cells. Conclusions Our study showed that continuous culture with cell immobilization is a valid approach for selecting cells adapted to hydrogen peroxide. Elucidation of H2O2 adaptation mechanisms in HPR2 could be helpful to develop oxygen resistant bifidobacteria.

  14. High-Pass Filtering at Vestibular Frequencies by Transducer Adaptation in Mammalian Saccular Hair Cells

    Songer, Jocelyn E.; Eatock, Ruth Anne


    The mammalian saccule detects head tilt and low-frequency head accelerations as well as higher-frequency bone vibrations and sounds. It has two different hair cell types, I and II, dispersed throughout two morphologically distinct regions, the striola and extrastriola. Afferents from the two zones have distinct response dynamics which may arise partly from zonal differences in hair cell properties. We find that type II hair cells in the rat saccular epithelium adapt with a time course appropriate for influencing afferent responses to head motions. Moreover, striolar type II hair cells adapted by a greater extent than extrastriolar type II hair cells and had greater phase leads in the mid-frequency range (5-50 Hz). These differences suggest that hair cell transduction may contribute to zonal differences in the adaptation of vestibular afferents to head motions.

  15. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses.

    Lian, Jeffrey; Luster, Andrew D


    The generation of adaptive immune responses occurs in the lymph node (LN) and requires that lymphocytes locate and interact with cognate antigen-bearing dendritic cells. This process requires the coordinated movement of both innate and adaptive immune cells, and is orchestrated by the chemokine family of chemotactic cytokines. Upon initiation of inflammation, the LN undergoes dramatic changes that include the marked induction of specific chemokines in distinct regions of the reactive LN. These chemokine rich domains establish LN niches that facilitate the differentiation of CD4+ T cells into effector cell subsets and the rapid activation of memory CD8+ T cells. This review will focus on recent advances highlighting the importance of LN chemokines for shaping adaptive immune responses by controlling immune cell migration, positioning, and interactions in the reactive LN. PMID:26067148

  16. Characterization of adaptation motors in saccular hair cells by fluctuation analysis.

    Frank, Jonathan E.; Markin, Vladislav; Jaramillo, Fernán


    The mechanical sensitivity of hair cells, the sensory receptors of the vestibular and auditory systems, is maintained by adaptation, which resets the transducer to cancel the effects of static stimuli. Adaptation motors in hair cells can be experimentally activated by externally applying a transduction channel blocker to the hair bundle, causing the hair bundle to move in the negative direction. We studied the variance in the position of the hair bundle during these displacements and found th...

  17. Impact of host cell line adaptation on quasispecies composition and glycosylation of influenza A virus hemagglutinin.

    Jana Verena Roedig

    Full Text Available The genome of influenza A viruses is constantly changing (genetic drift resulting in small, gradual changes in viral proteins. Alterations within antibody recognition sites of the viral membrane glycoproteins hemagglutinin (HA and neuraminidase (NA result in an antigenetic drift, which requires the seasonal update of human influenza virus vaccines. Generally, virus adaptation is necessary to obtain sufficiently high virus yields in cell culture-derived vaccine manufacturing. In this study detailed HA N-glycosylation pattern analysis was combined with in-depth pyrosequencing analysis of the virus genomic RNA. Forward and backward adaptation from Madin-Darby Canine Kidney (MDCK cells to African green monkey kidney (Vero cells was investigated for two closely related influenza A virus PR/8/34 (H1N1 strains: from the National Institute for Biological Standards and Control (NIBSC or the Robert Koch Institute (RKI. Furthermore, stability of HA N-glycosylation patterns over ten consecutive passages and different harvest time points is demonstrated. Adaptation to Vero cells finally allowed efficient influenza A virus replication in Vero cells. In contrast, during back-adaptation the virus replicated well from the very beginning. HA N-glycosylation patterns were cell line dependent and stabilized fast within one (NIBSC-derived virus or two (RKI-derived virus successive passages during adaptation processes. However, during adaptation new virus variants were detected. These variants carried "rescue" mutations on the genomic level within the HA stem region, which result in amino acid substitutions. These substitutions finally allowed sufficient virus replication in the new host system. According to adaptation pressure the composition of the virus populations varied. In Vero cells a selection for "rescue" variants was characteristic. After back-adaptation to MDCK cells some variants persisted at indifferent frequencies, others slowly diminished and even

  18. File list: His.Adl.20.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Full Text Available His.Adl.20.AllAg.Temperature_sensitive_cells dm3 Histone Adult Temperature ...

  19. File list: His.Adl.05.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Full Text Available His.Adl.05.AllAg.Temperature_sensitive_cells dm3 Histone Adult Temperature ...

  20. File list: His.Adl.50.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Full Text Available His.Adl.50.AllAg.Temperature_sensitive_cells dm3 Histone Adult Temperature ...

  1. File list: His.Adl.10.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Full Text Available His.Adl.10.AllAg.Temperature_sensitive_cells dm3 Histone Adult Temperature ...

  2. File list: Unc.Unc.10.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Unc.10.Unclassified.AllCell sacCer3 Unclassified Unclassified Unclassified http...:// ...

  3. File list: Unc.Kid.50.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Kid.50.Unclassified.AllCell mm9 Unclassified Unclassified Kidney SRX1116348,SRX...1116347 ...

  4. File list: Unc.Adp.10.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Adp.10.Unclassified.AllCell hg19 Unclassified Unclassified Adipocyte SRX813776,...SRX813777 ...

  5. File list: Unc.Adp.20.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Adp.20.Unclassified.AllCell hg19 Unclassified Unclassified Adipocyte SRX813777,...SRX813776 ...

  6. File list: Unc.Kid.50.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Kid.50.Unclassified.AllCell hg19 Unclassified Unclassified Kidney SRX130265,SRX...8 ...

  7. File list: Unc.Lar.50.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Lar.50.Unclassified.AllCell ce10 Unclassified Unclassified Larvae SRX657408 htt...p:// ...

  8. File list: Unc.Adp.05.Unclassified.AllCell [Chip-atlas[Archive

    Full Text Available Unc.Adp.05.Unclassified.AllCell hg19 Unclassified Unclassified Adipocyte SRX813776,...SRX813777 ...

  9. On-Chip Quantitative Measurement of Mechanical Stresses During Cell Migration with Emulsion Droplets

    Molino, D.; S. Quignard; Gruget, C.; Pincet, F.; Y. Chen; Piel, M.; Fattaccioli, J.


    The ability of immune cells to migrate within narrow and crowded spaces is a critical feature involved in various physiological processes from immune response to metastasis. Several in-vitro techniques have been developed so far to study the behaviour of migrating cells, the most recent being based on the fabrication of microchannels within which cells move. To address the question of the mechanical stress a cell is able to produce during the encounter of an obstacle while migrating, we devel...

  10. File list: Oth.ALL.50.mre-11.AllCell [Chip-atlas[Archive

    Full Text Available Oth.ALL.50.mre-11.AllCell ce10 TFs and others mre-11 All cell types SRX494877,SRX49...4868,SRX494867 ...